Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

226 records · Page 13Linked to original sources

PubMedDate not supplied

[The influence of experimental traffic noise on autonomous functions of normotensives and hypertensives after stress (author's transl)].

In a series of experiments on 12 normotensives and 12 essential hypertensives the influence of traffic noise (81 dB) on autonomous functions after stress exposure was examined. The process of the stress reaction was started by visually presented arithmetic tasks under affecting noise. With normotensives and hypertensives this combination of stressors led to a significant increase of the systolic and diastolic blood pressure, heart rate, and muscle tone. The influence of traffic noise directly following the combination of stressors was examined in an intraindividual comparison with a resting-time period. During the period of noise, significantly higher values with blood pressure data only were found with normotensives and hypertensives as well. The comparison between the normotensive and the hypertensive group during the combination of stressors and during the following resting period showed no significant differences in reaction whereas during the second stressor hypertensives compared to normotensives showed strong, partly significant adaptation reactions of blood pressure with regard to the preceding experimental phase.

Adult↗

PubMedDate not supplied

Recruitment of a time-dependent inotropic reserve by postextrasystolic potentiation in normal and reperfused myocardium.

Impaired excitation-contraction coupling has been suggested as the underlying mechanism of postischemic contractile dysfunction of reperfused myocardium in in-vitro studies. To test this hypothesis in situ, postextrasystolic potentiation (PESP) following an extrasystole with constant prematurity and three different postextrasystolic time intervals (compensated, regular, abbreviated) was analyzed in 12 anesthetized dogs. Changes in regional inotropic state were assessed by comparison of end-systolic wall thickness (sonomicrometry) during PESP to the respective pressure-matched values of an end-systolic pressure/wall-thickness relationship established during brief manual clamping of the aorta. Before ischemia, posterior end-systolic wall-thickness was increased by 0.19 +/- 0.35 (SD) mm during PESP with an abbreviated, by 0.36 +/- 0.42 mm with a regular, and by 0.60 +/- 0.42 mm with a compensated postextrasystolic interval. Baseline systolic wall thickening was decreased from 16.2 +/- 5.4% (before ischemia) to -3.0 +/- 3.4% at the end of 15 min left circumflex coronary occlusion, and to 2.8 +/- 7.5% at 10 min, 7.2 +/- 3.9% at 4 h, and 7.9 +/- 4.1% at 8 h reperfusion. Stepwise increases in regional inotropic state during PESP with increasing postextrasystolic intervals were not different in normal and reperfused myocardium. Thus, excitation-contraction coupling appears not to be impaired during inotropic stimulation of reperfused myocardium in situ.

Animals↗

PubMedDate not supplied

Evaluation of parameters for the assessment of regional myocardial contractile function during asynchronous left ventricular contraction.

The primary purpose of this study was to evaluate parameters used for the measurement of regional myocardial contractile function in the setting of left ventricular (LV) asynchrony. Secondarily, we tested whether the peak negative value of left ventricular dP/dt (-dP/dt) can be used to estimate global LV end-systole during asynchrony. In seven anesthetized (Isoflurane) swine the left anterior descending coronary artery was cannulated and perfused at constant blood flow rates. To produce LV asynchrony, dobutamine (D) was infused into the perfusion system. This was repeated later during coronary hypoperfusion (HYPO) sufficient to produce regional contractile dysfunction. The amount of LV wall thickening during systole (% WT, sonomicrometry) was calculated using either -dP/dt or the closure of the aortic valve (AO, electromagnetic flow probe) for estimating the timing of global LV end-systole. % WT was compared to other parameters which are not dependent upon the timing of global LV end-systole, including the amplitude of the first harmonic of the Fourier transform (AMP) and regional myocardial work (WI) estimated form the left ventricular pressure-wall thickness relationship. A close correlation between global LV end-systole defined by the AO or -dP/dt existed during control, D or HYPO. During HYPO + D no such relationship was found (r = .22, NS), and % WT calculated using -dP/dt as an estimate of end-systole was underestimated when compared to % WT calculated by use of the AO to estimate end-systole (2.9 +/- 6.8% vs 6.3 +/- 6.6%, p less than .05). % WT, AMP, and WI showed similar results during control, D and HYPO. However, During HYPO increased the AMP from .59 +/- .23 mm to .76 +/- .32 mm and WI from 67 +/- 20 mm Hg*mm to 95 +/- 24 mm Hg*mm (p less than .05), respectively. This increase in regional myocardial function, however, was not detected by % WT (10.5 +/- 6.4% vs 6.3 +/- 6.6%). Thus, during left ventricular asynchrony, the measurement of LV -dP/dt to estimate the timing of global LV end-systole is inappropriate and can lead to inaccuracies in the measurement of regional contractile function. Parameters such as AMP or WI are advantageous since global LV end-systole does not need to be accurately defined.

Animals↗

PubMedDate not supplied

Effects of heart rate on hemodynamic severity of coronary artery stenosis in the dog.

In 14 open-chest mongrel dogs, the effects of heart rate on hemodynamic severity of proximal coronary artery stenosis were studied. Stenosis was produced by a circumferential wire snare on left circumflex coronary artery. An intermediate stenosis was defined by reduction of peak reactive hyperemia response to 200% of control flow, a critical stenosis by prevention of any reactive hyperemia flow to a 15-s occlusion. Heart rate was increased stepwise from control to 160 and 200 beats/min by left atrial pacing. In intermediate stenosis, increased pacing rate reduced peripheral coronary pressure distal to the stenosis from 77 +/- 3 to 73 +/- 4 to 65 +/- 3 mm Hg (p less than 0.05) and increased stenosis resistance from 0.30 +/- 0.05 to 0.34 +/- 0.05 to 0.35 +/- 0.05 resistance units (p less than 0.05). In critical stenosis, increased heart rate changed peripheral coronary pressure from 45 +/- 5 to 49 +/- 5 to 48 +/- 5 mm Hg (p less than 0.01) and reduced stenotic resistance from 1.24 +/- 0.19 to 1.08 +/- 0.18 to 1.15 +/- 0.19 resistance units (p less than 0.005). A significant correlation between changes in stenotic resistance and peripheral coronary pressure was obtained (r = -0.71, p less than 0.001). In maximally dilated coronary arteries, a circumferential stenosis decreased circumflex artery flow to 50%. Increased pacing rate up to nearly 200 beats/min raised peripheral coronary pressure distal to the stenosis from 51 +/- 4 to 56 +/- 4 mm Hg (p less than 0.005) and changed stenotic resistance from 0.41 +/- 0.13 to 0.30 +/- 0.06 to 0.33 +/- 0.10 resistance units (p less than 0.05). It is assumed that the changes in peripheral coronary pressure alter the luminal area of the stenosis and hence calculated stenotic resistance. Other possible mechanisms like turbulent streaming, vasomotion or platelet aggregation appear to be of minor importance in the present experimental conditions.

Animals↗

PubMedDate not supplied

The relationship between regional blood flow and contractile function in normal, ischemic, and reperfused myocardium.

The prevailing paradigm of coronary physiology and pathophysiology is that a balance between blood flow (i.e., supply) and function (i.e., demand) exists under normal conditions and that an imbalance between supply and demand occurs during ischemia. However, this paradigm is derived largely from studies relating changes in total coronary inflow to global ventricular function. The present article examines the relationship between myocardial blood flow and function on a regional level and proposes that a change may be needed in the current paradigm of coronary pathophysiology. In normal myocardium, considerable heterogeneity of regional blood flow exists, indicating either similar heterogeneity of metabolic demand and function or questioning the precision of metabolic coupling between flow and function. After the onset of ischemia, a transient imbalance between the reduced blood flow and function may exist. However, myocardial function rapidly declines and during early steady-state ischemia regional myocardial blood flow and function are once again evenly matched. Such supply-demand balance may persist over prolonged periods of ischemia enabling the myocardium to remain viable through reduction of energy expenditure for contractile function, i.e., to "hibernate". Whereas in "hibernating" ischemic myocardium, regional myocardial blood flow and function are both reduced but appropriately matched to one another, flow and function appear to be largely uncoupled in reperfused "stunned" myocardium. The clinical identification of viable but ischemic (hibernating) and postischemic (stunned) myocardium is of utmost importance in patients undergoing reperfusion procedures. A new paradigm of coronary and myocardial pathophysiology, encompassing a regional as well as a global view of perfusion and function, will have to include explanations for phenomena such as myocardial hibernation and myocardial stunning.

Animals↗

PubMedDate not supplied

Effect of coronary hyperperfusion on regional myocardial function and oxygen consumption of stunned myocardium in pigs.

The "Gregg phenomenon" implies that myocardial function and oxygen consumption (MVO2) increase when coronary perfusion is enhanced within or above the autoregulatory range. We have recently demonstrated that the "Gregg phenomenon" has no significance for regional myocardial function and MVO2 in anesthetized swine in situ. There is, however, some evidence that the "Gregg phenomenon" may exist within stunned myocardium. To test whether coronary hyperperfusion increases regional myocardial function and MVO2 in stunned myocardium, in six anesthetized swine the left anterior descending coronary artery (LAD) was cannulated and perfused at constant pressure (CAP) using an extracorporal circuit. The coronary vein which parallels the LAD was cannulated to allow measurement of regional MVO2 and regional systolic wall thickening (WT%) of the anterior myocardium was assessed using sonomicrometry. Blood flow (CBF) to the LAD was increased by increasing CAP within the extracorporal circuit or by intracoronary adenosine infusion (150 micrograms/min). In normal myocardium, increasing CBF from 71.4 +/- 19.7 (SD) to 156.7 +/- 48.8 ml/min/100 g by increasing CAP from 100 +/- 10 to 190 +/- 10 mm Hg or increasing CBF from 75.1 +/- 29.1 to 189.2 +/- 45.8 ml/min/100 g by intracoronary adenosine infusion did not increase WT% (34.3 +/- 12.2% vs 32.1 +/- 10.6% and 32.3 +/- 10.7% vs 30.1 +/- 13.2%, respectively). MVO2 was not changed during enhanced CAP (6.94 +/- 1.05 vs 8.10 +/- 1.08 ml/min/100 g) and during intracoronary adenosine infusion (6.67 +/- 1.45 vs 7.30 +/- 2.23 ml/min/100 g). Twenty min of hypoperfusion followed by 30 min of reperfusion depressed WT% by 47% (p less than 0.05). However, MVO2 was only decreased by 23% (NS). In the stunned myocardium, increasing CBF from 62.1 +/- 36.4 to 157.1 +/- 60.0 ml/min by increasing CAP was not associated with an increase in WT%. MVO2, however, increased from 5.14 +/- 1.07 to 8.88 +/- 1.83 ml/min/100 g (p less than 0.05). Comparable results were achieved when CBF was increased from 60.3 +/- 28.7 to 176.9 +/- 48.5 ml/min by intracoronary adenosine infusion. WT% was unaffected, while MVO2 increased from 4.69 +/- 0.92 to 9.46 +/- 3.39 ml/min/100 g (p less than 0.05). Thus, increasing coronary perfusion within or above the autoregulatory range increases MVO2 in stunned myocardium, but without a simultaneous increase in regional myocardial function.

Adenosine↗

PubMedDate not supplied

Coronary microembolization.

Atherosclerotic plaque rupture is a key event in the pathogenesis of acute coronary syndromes and during coronary interventions. Atherosclerotic plaque rupture does not always result in complete thrombotic occlusion of the entire epicardial coronary artery with subsequent acute myocardial infarction; however, in milder forms it may result in the embolization of atherosclerotic and thrombotic debris into the coronary microcirculation. The present report summarizes the available morphologic evidence for coronary microembolization in patients who died of coronary artery disease, especially sudden death. The report then goes on to address the experimental pathophysiology of coronary microembolization in animal models of acute coronary syndromes and heart failure. Finally, the report presents the available clinical evidence for coronary microembolization, highlights its key features--arrhythmias, contractile dysfunction, infarctlets and reduced coronary reserve--and addresses prevention by mechanical protection devices and glycoprotein IIb/IIIa antagonism.

Animals↗

PubMedDate not supplied

Nifedipine prevents sympathetic vasoconstriction distal to severe coronary stenoses.

Cardiac sympathetic nerve stimulation ( CSNS ) can induce vasoconstriction distal to severe coronary stenoses by activation of vascular alpha 2-adrenoceptors. Whether nifedipine can antagonize this CSNS -induced vasoconstriction was tested in 11 anesthetized, vagotomized dogs. CSNS decreased the end-diastolic resistance of intact coronary arteries from 0.76 +/- 0.07 to 0.56 +/- 0.05 mm Hg x min x 100 g/ml (p less than 0.05). In contrast, the resistance distal to severe stenoses, which were defined by a reduction of the postocclusive reactive hyperemia to almost zero, was increased during CSNS from 0.52 +/- 0.06 to 0.87 +/- 0.14 mm Hg x min x 100 g/ml (p less than 0.05). This increase in resistance was associated with severe ischemia, as indicated by a net lactate production of the circumflex-perfused myocardium and a decrease in systolic segment shortening from 8.4 +/- 0.7 to 7.0 +/- 0.7% (p less than 0.05). Both intracoronary (10 micrograms) and intravenous (10 micrograms/kg) administration of nifedipine did not change the poststenotic resistance at rest, but did prevent the CSNS -induced increase in resistance, the decrease in regional contraction, and the net lactate production. We conclude that nifedipine can prevent the deleterious role of alpha-adrenoceptor-mediated vasoconstriction in the genesis of myocardial ischemia.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Alpha 1- and alpha 2-adrenoceptor-mediated vasoconstriction of large and small canine coronary arteries in vivo.

The role of alpha-adrenoceptor subtypes mediating vasoconstriction of large epicardial and small resistive coronary arteries was investigated in 26 open-chest dogs. The left circumflex coronary artery was perfused at a constant pressure. Large vessel vasomotion was determined by measurement of circumflex coronary arterial diameter (ultrasonic transit-time technique); the vasomotion of the small resistive coronary arteries was determined from calculated end-diastolic circumflex artery resistance. beta-Receptors were blocked by propranolol (2 mg/kg i.v.) and both vagal nerves were cut. In eight dogs, the intracoronary administration of the alpha 1-adrenoceptor agonist methoxamine (500 micrograms) increased calculated large vessel resistance by 18.8 +/- 5.7% and end-diastolic resistance by 9.5 +/- 0.3%. Intracoronary administration of the alpha 2-adrenoceptor agonist BHT 920 (500 micrograms) did not affect large vessel resistance, but increased end-diastolic resistance by 37.5 +/- 5.6%. In an additional 18 dogs, left cardiac sympathetic nerve stimulation induced an increase in large vessel resistance by 11.1 +/- 0.9% and in end-diastolic resistance by 31.8 +/- 3.0%. The increase in large vessel resistance was prevented by the alpha 1-adrenoceptor antagonist prazosin (1.2 mg/kg i.v.), which still permitted an increase in end-diastolic resistance by 23.0 +/- 3.2%. The increase in end-diastolic resistance was prevented by the alpha 2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.), which still permitted an increase in large vessel resistance by 11.9 +/- 2.4%. The calcium antagonist nifedipine (20 micrograms/kg i.v.) prevented both the increase in large vessel resistance and end-diastolic resistance during sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Clonidine prevents the sympathetic initiation and aggravation of poststenotic myocardial ischemia.

We studied the effects of clonidine (10 micrograms/kg i.v.) on the positive feedback between poststenotic myocardial ischemia and cardiac sympathetic nerve activation and on the initiation of poststenotic myocardial ischemia during bilateral carotid occlusion in 12 anesthetized, open-chest dogs. During 20 min of acute severe coronary stenosis, cardiac sympathetic nerve activity increased by 24 +/- 6%, poststenotic coronary resistance increased from 0.45 +/- 0.05 to 0.61 +/- 0.08 mm Hg . min . 100 g/ml, and the poststenotic myocardial lactate consumption of 25 +/- 6 mumol/min . 100 g at 1 min of stenosis was reversed to a net lactate production of 8 +/- 3 mumol/min . 100 g after 20 min of stenosis. An additional 60-s bilateral carotid occlusion increased cardiac sympathetic nerve activity furthermore to 157 +/- 7% of control, increased poststenotic coronary resistance to 0.84 +/- 0.14 mm Hg . min . 100 g/ml, and increased the net lactate production to 22 +/- 6 mumol/min . 100 g. With heart rate and left ventricular pressure kept constant, clonidine decreased cardiac sympathetic nerve activity to 21 +/- 6% of control and prevented any further sympathetic activation during 20 min of coronary stenosis and bilateral carotid occlusion. Conversely, poststenotic coronary resistance and myocardial lactate consumption remained unchanged. Intracoronary clonidine (100 micrograms) in five of the 12 dogs increased poststenotic coronary resistance from 0.47 +/- 0.04 to 0.61 +/- 0.05 mm Hg . min . 100 g/ml and reversed the myocardial lactate consumption of 36 +/- 4 mumol/min . 100 g to a net lactate production of 7 +/- 5 mumol/min . 100 g. Our results suggest that clonidine can, by a central nervous action, prevent the sympathetic initiation and aggravation of poststenotic myocardial ischemia and may thus be effective in the treatment of exertional angina.

Animals↗