Search PubMed⌕ Search

Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

At least 145 records · Page 8Linked to original sources
PubMed1994

Attenuation of myocardial stunning by the ACE inhibitor ramiprilat through a signal cascade of bradykinin and prostaglandins but not nitric oxide.

BACKGROUND: Attenuation of myocardial stunning by several angiotensin-converting enzyme (ACE) inhibitors has been demonstrated. However, the signal cascade mediating such protective effect has not been analyzed in detail so far. METHODS AND RESULTS: In a first protocol, we addressed the role of bradykinin and analyzed the effect of the ACE inhibitor ramiprilat without and with added bradykinin B2 receptor antagonist HOE 140 on regional myocardial blood flow (colored microspheres) and function (sonomicrometry). Thirty-two enflurane/N2O-anesthetized open-chest dogs were subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCx) and 4 hours of subsequent reperfusion. Eight dogs served as placebo controls (group 1), and 8 dogs received ramiprilat (20 micrograms/kg IV) before LCx occlusion (group 2). Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL.min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4). Mean aortic pressure was kept constant with an intra-aortic balloon, and heart rate did not change throughout the experimental protocols. Under control conditions and during myocardial ischemia, posterior transmural blood flow (BF) and systolic wall thickening (WT) were not different in the four groups of dogs. However, at 4 hours of reperfusion, WT was still depressed in groups 1 (-10 +/- 20% of control [mean +/- SD]), 3 (-18 +/- 12% of control), and 4 (-12 +/- 21% of control), whereas WT in group 2 had recovered to 55 +/- 20% of control (P < .05 versus group 1). BF at 4 hours of reperfusion was not different in the four groups of dogs. Thus, the beneficial effect of ramiprilat on the functional recovery of stunned myocardium was obviously mediated by bradykinin. Since bradykinin stimulates the formation of both prostaglandins and nitric oxide, we tested in a second protocol which of these mediators was further involved in the beneficial effects of ramiprilat. Twenty-four additional dogs were subjected to 15 minutes of LCx occlusion and 4 hours of reperfusion. Six dogs received the cyclooxygenase inhibitor indomethacin (10 mg/kg IV) (group 5) and 6 dogs a combination of indomethacin with ramiprilat (group 6) before LCx occlusion. Six dogs received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg IV) (group 7) and 6 dogs a combination of L-NAME with ramiprilat (group 8) before LCx occlusion. BF and WT before and during myocardial ischemia were not different in groups 5 and 6 and groups 7 and 8. However, at 4 hours of reperfusion, WT was still depressed in groups 5 (-10 +/- 38% of control), 6 (-7 +/- 18% of control), and 7 (-12 +/- 14% of control), whereas WT in group 8 had recovered to 47 +/- 28% of control (P < .05 versus group 7). BF at 4 hours of reperfusion was not different in the four groups of dogs. CONCLUSIONS: In summary, the attenuation of stunning by the ACE inhibitor ramiprilat involves a signal cascade of bradykinin and prostaglandins but not nitric oxide.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

[Does the choice of a reference system modify the analysis of ergospirometric values?].

The importance of the reference system (arbitrary abscissa units) for the analysis of the time courses of cardiopulmonary exercise test indices was assessed. Ten untrained students, 10 athletes, and 10 triathletes performed an exhaustion-limited cycling test. The courses of 20 pulmonary and hemodynamic indices were investigated with respect to the reference systems "heart rate," "relative and absolute oxygen consumption," "power," and a newly developed index "power-duration-product." Most of the significant differences were observed by reference to the power-duration-product. When using the power-duration-product as reference, the courses of eight indices differed significantly between students and triathletes, the courses of five indices between students and athletes, and the course of one index between athletes and triathletes. Since the number of the significant differences between the groups, as well as the courses themselves, depended clearly on the underlying reference system, the choice of the reference system must be considered as an important determinant for the analysis of cardiopulmonary exercise tests.

Adult↗
PubMed1994

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischemia is still ongoing, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery whereas in stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunction myocardium but also to distinguish hibernating and stunned myocardium. The only causal therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since by definition blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning involves large parts of the left ventricle and thus impairs global left ventricular function, the extent of myocardial stunning can be reduced by inotropic stimulation, without inducing further damage to the myocardium. In the experimental setting, antioxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischemia.

Adenosine Triphosphate↗
PubMed1993

Local and neurohumoral control of coronary blood flow.

The powerful local metabolic regulation adjusting coronary blood flow to myocardial oxygen consumption under normal conditions is beyond doubt. However, despite substantial experimental efforts the responsible mediators are still largely unknown. Adenosine, a purported mediator of local metabolic control of coronary blood flow, is probably only involved in transient flow adaptations, but not in steady-state coronary autoregulation. Even below the autoregulatory range a substantial vasodilator reserve persists. Recruitment of such vasodilator reserve results in improved regional myocardial blood flow and attenuated regional ischemic dysfunction. beta-adrenergic coronary dilation is of minor functional importance. alpha-adrenergic coronary constriction acts to attenuate increases in coronary blood flow during sympathetic activation under normal conditions, such that myocardial oxygen extraction increases to match the increased oxygen consumption. alpha-adrenergic coronary constriction remains operative in ischemic myocardium, thus precipitating or contributing to acute myocardial ischemia during sympathetic activation and exercise in experimental animals as well as in patients with stable angina. The vagal transmitter acetylcholine--upon exogenous intracoronary infusion--induces critical constriction of epicardial coronary arteries with endothelial dysfunction and atherosclerosis. However, a vagal initiation of coronary spasm or myocardial ischemia has not been documented so far. Similarly, peptide hormones/transmitters such as NPY, vasopressin, and angiotensin can induce myocardial ischemia upon exogenous administration. Their pathophysiological role in myocardial ischemia and reperfusion, however, remains to be established.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

CORDAT II: a new program for data acquisition and on-line calculation of hemodynamic and regional myocardial dimension parameters.

The present paper describes a new computer program for data acquisition and on-line evaluation of hemodynamic parameters. The hardware setup is based on a standard i486 personal computer equipped with an analog to digital converter and an additional display controller. During data acquisition the multitasking program automatically detects the beginning and the end of a cardiac cycle. Immediately after the recognition of a cardiac cycle the program calculates and displays user-defined hemodynamic parameters and mean values over a given time or a given number of beats. There is a high correlation between manually determined hemodynamic parameters and the parameters determined automatically by CORDAT II.

Aorta↗
PubMed1993

Transcutaneous pCO2-monitoring for the evaluation of the anaerobic threshold. Comparison to lactate and ventilatory thresholds.

The monitoring of transcutaneous pCO2 (pCO2(tc) is an alternative to the invasive determination of the anaerobic threshold by analysis of arterial lactate concentration or to the uncomfortable determination of the ventilatory threshold. We compared the threshold determination by pCO2(tc)-monitoring to the 4 mmol/l lactate threshold and to the ventilatory threshold (point where the ventilatory equivalent of oxygen started to increase continuously) in 15 athletes during cycle exercise. The first distinct deflection point in the pCO2(tc) time course after the start of exercise was chosen to indicate the anaerobic threshold. The mean threshold determined by pCO2(tc) occurred at the same workload as the ventilatory threshold but at a lower workload than the lactate threshold. In spite of the good correspondence in the respective means there was a wide range of individual differences between the pCO2(tc) derived thresholds and both reference thresholds. Thus, looking at an individual, the continuous monitoring of the pCO2(tc) does not provide reliable data on the occurrence of the transition from aerobic to anaerobic metabolism.

Adolescent↗
PubMed1993

A proischaemic action of nisoldipine: relationship to a decrease in perfusion pressure and comparison to dipyridamole.

OBJECTIVE: The calcium antagonist nisoldipine has recently been reported to induce rather than to attenuate ischaemia in some patients with stable angina. The aim of the study was to investigate the mechanisms underlying this proischaemic effect. METHODS: In 20 anaesthetised dogs systemic haemodynamic variables, regional myocardial blood flow (coloured microspheres), and systolic wall thickening (sonomicrometry) were measured during control conditions and following severe stenosis on the left circumflex coronary artery, before and after intravenous administration of equihypotensive doses of either nisoldipine (group I, n = 10) or dipyridamole (group II, n = 10). Finally, measurements were performed while the drug induced decreases in mean aortic pressure--18 (SD 6) mmHg in group I and 14(6) mm Hg in group II--were reversed by inflation of an intra-aortic balloon. RESULTS: The stenosis decreased posterior wall thickening to 50% of control, and posterior subendocardial blood flow from 1.48(0.27) to 0.61(0.19) ml.min-1.g-1 in group I and from 1.49(0.23) to 0.62(0.18) ml.min-1.g-1 in group II. Subendocardial blood flow was further decreased after administration of either nisoldipine [0.37(0.20) ml.min-1.g-1, p < 0.05 v stenosis] or dipyridamole [0.22(0.11) ml.min-1.g-1, p < 0.05 v stenosis]. Regional myocardial blood flow in the anterior region was increased. The drug induced reduction of subendocardial blood flow decreased posterior wall thickening further from 9.3(2.1) to 6.2(3.9)% (p < 0.05 v stenosis, group I) and from 9.1(1.7) to 4.3(2.4)% (p < 0.05 v stenosis, group II). When the drug induced decrease in aortic pressure was reversed, subendocardial blood flow again increased in group I [0.63(0.19) ml.min-1.g-1, p < 0.05 v stenosis and nisoldipine] whereas in group II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and dipyridamole]. There was restoration of posterior wall thickening in group I [10.4(3.8)%, p < 0.05 v stenosis and nisoldipine], but not in group II [5.2(3.5)%, NS v stenosis and dipyridamole]. CONCLUSIONS: Nisoldipine and dipyridamole decrease subendocardial blood flow and contractile function distal to a severe stenosis when aortic pressure is decreased. No aggravation of ischaemia by nisoldipine is seen when hypotension is prevented. In contrast, dipyridamole in the absence of hypotension still induces a redistribution of flow at the expense of the ischaemic region.

Animals↗
PubMed1993

Post-ejection wall thickening as a marker of successful short term hibernation.

OBJECTIVE: Short term hibernating myocardium is characterised by a decrease in contractile function in proportion to the reduced blood flow, the recovery of creatine phosphate despite ongoing ischaemia, a recruitable inotropic reserve, and the absence of necrosis. During acute myocardial ischaemia systolic wall thickening decreases and post-ejection wall thickening develops. The extent of post-ejection thickening during severe ischaemia correlates with the recovery of contractile function during reperfusion. Whether the extent of post-ejection wall thickening can also distinguish short term hibernating myocardium from more severely ischaemic, infarcting myocardium and thus predict the amount of viable tissue was tested in 13 anaesthetised pigs. METHODS: The left anterior descending coronary artery (LAD) was cannulated and perfused at constant flow. After control measurements of regional myocardial blood flow (with radiolabelled microspheres) and wall thickening (sonomicrometry), coronary inflow was reduced to produce a reduction in regional contractile function by 60-100%. After 85 minutes of ischaemia, dobutamine was infused into the LAD for five minutes to determine the extent of inotropic reserve. Transmural biopsies were taken to measure regional myocardial creatine phosphate content and infarct size was determined after two hours of reperfusion by staining with triphenyl tetrazolium chloride. RESULTS: The extent of post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the myocardial creatine phosphate content (r = 0.812, n = 11, p < 0.01) and the extent of the dobutamine recruitable inotropic reserve (r = 0.783, n = 7, p < 0.05). A negative correlation existed between the extent of post-ejection wall thickening and % infarct size (r = -0.699, n = 10, p < 0.05 for the transmural piece of tissue containing the ultrasonic crystals; r = -0.743, n = 10, p < 0.05 for the area of the left ventricle at risk). Finally, post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the recovery of contractile function at 30 minutes reperfusion (r = 0.657, n = 10, p < 0.05). CONCLUSION: The extent of post-ejection wall thickening may indicate the amount of viable tissue after 85-90 minutes of low flow ischaemia. The greater the post-ejection wall thickening, the more myocardium is successfully hibernating.

Animals↗
PubMed1993

Heart rate variability and circulating catecholamine concentrations during steady state exercise in healthy volunteers.

OBJECTIVES: To assess whether exercise induced suppression of heart rate variability in the low frequency domain (0.06-0.15 Hz) is related to the increase in circulating catecholamine concentrations. DESIGN: Randomised crossover trial of three exercise tests characterised by different workloads. Pharmacological simulation of exercise-induced changes in vagal and sympathetic activity. PARTICIPANTS: Six healthy men with a mean age of 31.2 (SD 3.0) years. INTERVENTIONS: Three different workloads of steady state cycling ergometry: control state without cycling, cycling at a target heart rate of 100 beats/min, and cycling at a target heart rate of 150 beats/min. Intravenous infusion of atropine (target heart rate 100 beats/min) followed by the additional infusion of adrenaline and noradrenaline. MAIN OUTCOME MEASURES: Fast Fourier analysis of heart rate variability; blood pressure; and venous plasma concentrations of lactate, adrenaline, and noradrenaline. RESULTS: During the control exercise period there were no changes in the assessed variables compared with the preceding resting period. During exercise at a heart rate of 100 beats/min systolic blood pressure increased and heart rate variability decreased. During exercise at a heart rate of 150 beats/min systolic blood pressure and lactate, adrenaline, and noradrenaline concentrations increased. In addition, low frequency (LF) was lower than during exercise at 100 beats/min, high frequency (HF 0.15-0.80 Hz) resembled that during exercise at 100 beats/min, and diastolic blood pressure was reduced. Infusion of atropine caused no changes in blood pressure or plasma concentrations of lactate, adrenaline, and noradrenaline and decreased heart rate variability. The additional infusion of adrenaline and noradrenaline completely suppressed heart rate variability and increased blood pressure. CONCLUSIONS: The reduction in LF and HF during exercise at a heart rate of 100 beats/min, which is not characterised by increased plasma catecholamine concentrations, and during atropine infusion suggests that heart rate variability in the supine state is largely influenced by vagal activity. The additional reduction in LF during exercise at 150 beats/min and during catecholamine infusion may reflect a negative feedback of circulating catecholamines on the sympathetic control of heart rate.

Adult↗
PubMed1993

Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation.

BACKGROUND: Short-term hibernating myocardium is characterized by a decrease in contractile function in proportion to the reduced myocardial blood flow. Myocardial creatine phosphate content, initially decreased during the first minutes of ischemia, returns to near-control values, the ischemia-induced net lactate production is attenuated, and the myocardium remains viable despite ongoing hypoperfusion and contractile dysfunction. Hibernating myocardium after 85 minutes of ischemia maintains an inotropic reserve and responds to short-term intracoronary dobutamine infusion with increased work; however, this inotropic response is at the expense of metabolic recovery. We therefore hypothesized that the development of myocardial hibernation is a delicate process that is easily disturbed by unfavorable alterations in the oxygen-supply demand balance. METHODS AND RESULTS: To study the impact of prolonged inotropic stimulation on the development of myocardial hibernation, the left anterior descending coronary artery was cannulated and hypoperfused at constant flow in 12 enflurane-anesthetized swine. The reduction of coronary inflow was followed by a reduction of regional myocardial work (sonomicrometry) from 248 +/- 59 mm Hg.mm to 73 +/- 35 mm Hg.mm (P < .05) at 5 minutes of ischemia. Dobutamine (2.5 +/- 1 micrograms/min) was then infused for an additional 85 minutes. Work was increased at 5 minutes of dobutamine to 139 +/- 34 mm Hg.mm (P < .05 versus 5 minutes of ischemia). However, this increase was only transient, and after 85 minutes of dobutamine, work was decreased below the initial ischemic value (42 +/- 34 mm Hg.mm). At 5 minutes of ischemia, creatine phosphate content was reduced from 8.80 +/- 1.97 to 6.21 +/- 3.87 mumol/g wet wt, and myocardial ATP content was decreased slightly from 4.75 +/- 0.92 to 4.12 +/- 1.29 mumol/g wet wt (both, P = NS). After 5 minutes of dobutamine, further reductions in creatine phosphate content to 3.11 +/- 0.76 mumol/g wet wt and in ATP to 3.14 +/- 0.81 mumol/g wet wt were observed (both, P < .05 versus control). During the remainder of the continuous dobutamine infusion, creatine phosphate content remained unchanged, whereas ATP further decreased significantly to 1.68 +/- 0.96 mumol/g wet wt. The beta-adrenoceptor density of the left anterior descending coronary artery-perfused myocardium was 36.5 +/- 5.8 fmol (-)-[125I]iodocyanopindolol/mg protein under control conditions, and this was unchanged during ischemia and the subsequent dobutamine infusion. Following 90 minutes of ischemia with 85 minutes of dobutamine and 2 hours of reperfusion, infarct size (triphenyl tetrazolium chloride staining) was 26.3 +/- 7.5% of the area at risk. With constant hypoperfusion, dobutamine redistributed blood flow away from the subendocardium (0.20 +/- 0.08 versus 0.11 +/- 0.04 mL.min-1.g-1) toward the subepicardium (0.45 +/- 0.13 versus 0.51 +/- 0.21 mL.min-1.g-1) as well as to the right ventricle (0.26 +/- 0.08 versus 0.32 +/- 0.09 mL.min-1.g-1). Therefore, in two other groups of six and five swine, the severity of ischemia was increased to achieve an 80% or a 90% reduction in regional function, respectively, and the importance of the severity of blood flow reduction per se for the development of myocardial infarction was studied. The infarct size in the animals undergoing 85 minutes of dobutamine (26.3 +/- 7.5%) was increased above the level expected from the blood flow reduction alone (6.3 +/- 6.4%, P < .01). CONCLUSIONS: Both the increased severity of ischemia and the enhanced energy expenditure induced by dobutamine impair the development of myocardial short-term hibernation and precipitate myocardial infarction.

Animals↗
PubMed1993

Impact of alpha-adrenergic coronary vasoconstriction on the transmural myocardial blood flow distribution during humoral and neuronal adrenergic activation.

Increased heart rate and left ventricular pressure during humoral and neuronal adrenergic activation act to restrict blood flow preferentially in the subendocardium. The hypothesis was advanced that alpha-adrenergic coronary vasoconstriction preferentially in the subepicardium may counterbalance the enhanced extravascular compression in the subendocardium and serve to maintain blood flow transmurally uniform. In 40 anesthetized dogs, regional myocardial blood flow was determined with colored microspheres; wall function, with sonomicrometry. Humoral adrenergic activation (HAA) was induced by a combination of intravenous atropine, intravenous norepinephrine, and atrial pacing during baseline coronary vasomotor tone (group 1, n = 6) and in the presence of maximal coronary vasodilation with intravenous dipyridamole (group 2, n = 6). In an additional group, HAA was induced by intravenous norepinephrine in the presence of dipyridamole but without atropine and atrial pacing in order to increase end-diastolic left ventricular pressure (group 3, n = 6). Measurements were performed at rest, during HAA, and during ongoing HAA with the intracoronary infusion of the alpha-antagonist phentolamine (Phen). At unchanged mean aortic pressure, Phen improved blood flow particularly to the inner layers as follows: from 1.42 +/- 0.40 (mean +/- SD) to 1.90 +/- 0.40 mL/(min.g) (group 1, P < .05), from 4.99 +/- 2.31 to 5.53 +/- 2.56 mL/(min.g) (group 2, P < .05), and from 6.01 +/- 1.41 to 6.29 +/- 1.27 mL/(min.g) (group 3, P < .05), associated with a decrease in outer layer blood flow in groups 2 and 3. In 16 additional dogs, beta-adrenoceptors were blocked by propranolol and muscarinic receptors by atropine. Neuronal adrenergic activation (NAA) was induced by cardiac sympathetic nerve stimulation (CSNS) during baseline coronary vasomotor tone (group 4, n = 8) and in the presence of maximal vasodilation (group 5, n = 8). Measurements were performed at rest, during a first CSNS, and 20 minutes later during a second CSNS+Phen. The reproducibility of two consecutive episodes of CSNS 20 minutes apart was demonstrated in a separate set of experiments (n = 6). At matched mean aortic pressures, Phen improved blood flow to all myocardial layers in group 4, whereas in group 5, Phen induced a redistribution of myocardial blood flow toward subepicardial layers [from 4.44 +/- 0.96 to 4.81 +/- 0.83 mL/(min.g), P < .05] at the expense of inner layers. With the addition of Phen, there was no change in regional wall function in any group of dogs studied. Thus, during HAA, alpha-adrenergic coronary vasoconstriction does not exert a beneficial effect on transmural blood flow distribution. During NAA, a beneficial effect of alpha-adrenergic coronary vasoconstriction becomes apparent only under conditions of maximal coronary vasodilation.

Animals↗
PubMed1993

Regional blood flow and contractile function: are they matched in normal, ischemic and reperfused myocardium?

One central hypothesis of cardiovascular physiology has been a balance between myocardial blood flow and contractile function during natural conditions, i.e. supply and demand are matched. This hypothesis was derived from studies relating total coronary blood flow to global ventricular function. The present article examines the relationship between myocardial blood flow and function on a regional level. In normal myocardium, considerable heterogeneity of blood flow exists, indicating similar heterogeneity of metabolic demand and potentially also function. However, when the degree of metabolic coupling between flow and function is questioned, there is no evidence whether or not flow and function are matched on a regional level. One closely related hypothesis of cardiovascular pathology has been an imbalance or mismatch between supply and demand during ischemia. Because myocardial function rapidly declines during early ischemia, residual, regional myocardial blood flow and function may be once again matched on a lower level. Such low-level supply-demand balance may persist over prolonged periods of ischemia and permit the myocardium to remain viable, i.e. the myocardium can "hibernate." Analyzing myocardial blood flow and function on a regional level has generated new insight into strategies of adaptation to the adverse situation of reduced blood flow. Whereas in hibernating (ischemic) myocardium, regional myocardial blood flow and function are matched, flow and function appear to be unmatched in reperfused, dysfunctional, i.e. 'stunned' myocardium. "Stunned myocardium" appears once more as a result of a strategy of adaptation, as the preceding ischemia did not induce irreversible myocardial damage but preserved the ischemic myocardium viable, although functionally impaired.

Adaptation, Physiological↗
PubMed1993

[Chronic myocardial ischemia--hibernating myocardium: characteristics and limits].

Myocardial ischemia has traditionally been characterized as an imbalance between energy supply and demand. In the initial seconds after a sudden reduction of coronary blood flow, myocardial energy demand most certainly exceeds the reduced energy supply. This temporary mismatch, however, is an inherently unstable condition because regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function of the acutely ischemic myocardium are still poorly understood. If some residual blood flow exists, a state of "perfusion-contraction matching" can be maintained, at least for several hours, without the development of irreversible damage. A situation of persistent contractile failure in viable myocardium with normalizes upon reperfusion has been termed myocardial "hibernation". The metabolic status of such hypoperfused myocardium improves over the first few hours as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. The "hibernating" myocardium can respond to an inotropic stimulation by dobutamine with increased function. The recruitment of an inotropic reserve implies increased energy utilization. In fact, the partially normalized lactate production is again increased, and creatine phosphate is decreased again. Apparently the inotropic challenge once again precipitates a supply-demand imbalance which had been at least partially corrected by the ischemia-induced decrease of regional contractile function. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify "hibernating" myocardium. The development of such a delicate balance between energy supply and energy demand is easily disturbed by unfavorable alterations in the supply/demand ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Diastolic dysfunction of stunned myocardium.

The prolonged regional contractile failure of reperfused myocardium has usually been characterized in terms of systolic function, while only few reports on its diastolic function are available. None of these studies considered changes in the isovolumic diastole and the subsequent filling phase separately. Therefore, in the present study, the velocities of wall excursion during systole (Vsys), isovolumic diastole (Viso) and filling phase (Vfill) were determined in 12 anesthetized dogs. Additionally, post-ejection thickening (Pejt), a marker of left ventricular asynchrony, was determined. Measurements were performed under control conditions, during a 15 minute left circumflex (LCX) coronary artery occlusion (CAO) and at 10 minutes, 4 and 8 hours reperfusion. Heart rate, left ventricular pressure, and Vsys, Viso, Vfill, and Pejt of the anterior myocardium remained unchanged throughout the experiments. During CAO, systolic wall-thickening of the posterior wall was reversed to systolic wall-thinning. Upon reperfusion, Vsys started to recover (2.5 +/- 3.2 mm/s at 10 minutes) and gradually improved over 8 hours of reperfusion (4.6 +/- 3.2 mm/s at 4 hours, 6.4 +/- 1.5 mm/s at 8 hours). Viso became positive during CAO (9.4 +/- 7.1 mm/s vs. -5.6 +/- 3.9 mm/s under control conditions) and was unchanged at 10 minutes reperfusion (7.9 +/- 5.2 mm/s). After 4 hours and 8 hours of reperfusion, Viso recovered to 1.2 +/- 9.2 mm/s and -0.3 +/- 10.7 mm/s, respectively. Vfill also became positive during CAO (1.5 +/- 6.2 mm/s vs. -18 +/- 8.7 mm/s under control conditions). There was a quick recovery of Vfill (-9.4 +/- 7.5 mm/s) with the onset of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Time course and mechanisms of contractile dysfunction during acute myocardial ischemia.

BACKGROUND: The purpose of the study was to characterize the functional and metabolic adjustments of a myocardial region subjected to low-flow ischemia. In addition, studies tested whether such myocardium retains an inotropic reserve. METHODS AND RESULTS: Anesthetized swine were studied in which the left anterior descending coronary artery was cannulated and perfused at a constant low level causing regional contractile dysfunction (sonomicrometry for wall thickness) and the appearance of metabolic indicators of ischemia (decrease in creatine phosphate and lactate production) with only slight loss of ATP and glycogen (transmural biopsies). After 85 minutes of low-flow ischemia, dobutamine was infused into the hypoperfused artery as an inotropic challenge. Coronary hypoperfusion for 5 minutes resulted in a 54% reduction of regional systolic wall thickening, reversal of lactate consumption to lactate production, and a significant decrease in creatine phosphate. Subendocardial blood flow was reduced from 0.62 +/- 0.11 (+/- SD) to 0.16 +/- 0.07 mL.min-1.g-1. Prolonged hypoperfusion for 85 minutes resulted in no further change in regional blood flow but a partial recovery of metabolic parameters. Dobutamine infusion after 85 minutes of hypoperfusion increased regional myocardial work. However, again lactate production was significantly increase and creatine phosphate was decreased. Regional coronary hypoperfusion produces a downregulation of regional contractile function in proportion to the blood flow decrease. With prolonged hypoperfusion, after the initial adjustment phase, there is little further change in function, and metabolic markers of ischemia improve. Although the ischemic downregulated myocardium retains a significant inotropic reserve, primarily anaerobic energy production is utilized. CONCLUSIONS: These data are consistent with downregulation being a protective mechanism for the ischemic myocardium to restore an energy supply-demand balance in the face of reduced blood flow. Inotropic stimulation of the downregulated myocardium enhances regional function but at the cost of worsening its metabolic status. Thus, inotropic stimulation of the hypoperfused and downregulated myocardium is probably detrimental to long-term viability.

Acute Disease↗
PubMed1992

The power-duration product--evaluation of a new reference system for cardiopulmonary exercise testing.

The aim of this study was to assess the discriminatory power of the new reference system, power-duration product (PDP), for the analysis of haemodynamic and metabolic variables derived from cardiopulmonary exercise tests. The PDP was calculated as the cumulative index of the product of power (W) times the duration (minutes) of each individual exercise step. The study comprised 30 healthy male volunteers, who were classified into three groups with respect to their regular physical activity: 10 untrained medical students (students), 10 sprinters and long-jumpers (athletes) and 10 endurance athletes performing triathlon (triathletes). Twenty metabolic and haemodynamic variables were recorded throughout exhaustion-limited cycling ergometry. The data were analysed with respect to five reference systems (heart rate, relative and absolute oxygen consumption/body surface area, power, and PDP). A total of 14 differences between modified time courses of haemodynamic and metabolic variables in the three groups of volunteers were observed by reference to PDP, 12 by reference to relative oxygen consumption/body surface area, 11 by reference to heart rate, 8 by reference to absolute oxygen consumption/body surface area, and 7 by reference to power. When using PDP as the reference, the time courses of 8 parameters differed significantly between students and triathletes, 5 between students and athletes, and 1 between athletes and triathletes. In addition to its discriminatory superiority for the comparison of different groups characterized by different cardiopulmonary training and endurance, it was found that PDP permitted a better characterization of the individually performed exercise than the consideration of power per se.

Adolescent↗
PubMed1992

Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery. A model of short-term hibernation.

The regional, functional as well as metabolic consequences of inotropic stimulation on myocardium subjected to prolonged moderate ischemia were investigated. In 35 enflurane-anesthetized swine the left anterior descending coronary artery was cannulated and perfused at constant flow. The vein paralleling the left anterior descending coronary artery was cannulated for measurement of lactate and oxygen content. Transmural biopsies from the anterior myocardium were taken for the measurement of ATP, creatine phosphate, and glycogen. After control measurements, flow was adjusted to reduce regional contractile function (expressed as a work index, determined by sonomicrometry) by approximately 50%. After either 5, 25, 40, or 85 minutes of moderate ischemia, dobutamine was infused for 5 minutes into the ischemic region. In a separate group of five swine also subjected to 85 minutes of ischemia followed by infusion of dobutamine and 2 hours of reperfusion, triphenyltetrazolium chloride staining and light microscopy were used to identify infarcted tissue. Moderate ischemia (regional myocardial blood flow, 0.21 +/- 0.07 ml.min-1.g-1, determined by radiolabeled microspheres) was associated with a reduction of creatine phosphate after 5 minutes (from 9.35 +/- 2.54 to 6.43 +/- 1.06 mumol/g wet wt, p less than 0.05) and a further reduction after 25 minutes (3.18 +/- 0.69 mumol/g wet wt, p less than 0.05). Thereafter, creatine phosphate recovered despite continued ischemia (after 40 minutes, 4.95 +/- 1.37 mumol/g wet wt; after 85 minutes, 5.78 +/- 2.27 mumol/g wet wt). Lactate consumption during control conditions was reversed to production after 5 minutes of ischemia, which moderated during more prolonged ischemia. Without changing regional myocardial blood flow, infusion of dobutamine increased the work index significantly at any time point but also caused worsening of metabolic markers of ischemia. Nevertheless, even after 85 minutes of ischemia followed by the infusion of dobutamine and 2 hours of reperfusion, there was no evidence of necrosis. This experimental model provides a means of characterizing the mechanisms of short-term hibernation.

Animals↗