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Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

At least 109 records · Page 6Linked to original sources
PubMed1997

Association between hemodynamic parameters and the degeneration of sustained ventricular tachycardias into ventricular fibrillation in rats.

UNLABELLED: Sustained ventricular tachycardias (VT) often degenerate into ventricular fibrillation (VF). In the present study, the impact of VT on mean arterial blood pressure (MAP), myocardial blood flow (MBF), and myocardial oxygen consumption (MVCO2) was assessed. In addition, the degeneration of sustained VT into VF was analysed with respect to MAP. MBF was measured in 48 anesthetized rats with colored microspheres; arterial catecholamine levels were measured by HPLC in 16 additional rats during control conditions and VT. MBF (4. 66+/-1.29 ml/g/min; mean+/-s.d.) did not change with the onset of VT (5.37+/-1.92 ml/g/min, n.s.). Epinephrine (0.22+/-0.13 ng/ml) and norepinephrine (0.37+/-0.12 ng/ml) increased during VT (3.55+/-2.68 ng/ml, P<0.01; 0.88+/-0.44 ng/ml, P<0.05), respectively. VF was more frequent when MAP remained normal (MAP>80 mmHg: 26%) than with hypotension (MAP<80 mmHg: 2%, P<0.05). Mechanical failure was observed in 10% of rats with severe hypotension (MAP<60 mmHg), and 2% with moderate hypotension (MAP 60-80 mmHg). The endo-epicardial MBF ratio in the VF group was significantly lower than that in the non-VF group (0.94+/-0.17 v 1.11+/-0.24, P<0.05). CONCLUSIONS: severe hypotension predisposes to the occurrence of acute mechanical failure during VT; moderate hypotension during VT, however, serves as a protective mechanism against VF in structurally normal hearts. Subendocardial hypoperfusion in the presence of an increased energy demand during VT is suggested to be responsible for the initiation of VF.

Animals↗
PubMed1997

[New developments in parameter-oriented roentgen densitometry perfusion analysis within the scope of heart catheter studies].

X-ray densitometric evaluation of digital subtraction coronary arteriograms allows a qualitative and quantitative detection of contrast medium propagation through the epicardial coronary arteries, the capillary system and the coronary venous system. So-called "time-density-curves" (TDCs) can be generated following Lambert-Beer's law similar to indicator dilution curves by using contrast medium as the indicator. Several time and density parameters can be derived from these TDCs, which are related to local myocardial perfusion. Different animal validation studies have shown the applicability of this concept for in-vivo evaluation of coronary blood flow and myocardial perfusion. Nevertheless, absolute measurement of volumetric coronary blood flow or myocardial perfusion failed. Therefore, relative changes in coronary blood flow or myocardial perfusion in response to pharmacologically induced maximum hyperemia were measured and coronary or myocardial perfusion reserve was calculated as the ratio of hyperemic flow or perfusion divided by baseline values. Despite theoretical attractions for an application during routine cardiac catheterization, this densitometric approach did not get a wide acceptance. Primary reason for this limited use in specialized centers was the time consuming process of densitometric evaluation of the subtraction coronary arteriograms, which require digital cine angiography and necessitates enormous computer hard ware. This main limitation has been overcome since more powerful computer hard ware (processor speed, hard disk space, digitization boards) has become rapidly available during the last years at more moderate pricing and digital techniques today are state of the art in cardiac catheterization laboratories. In addition, soft ware program packages allowed an automatization of the digitization and densitometric evaluation process. These programs include ECG triggered cine image digitization with improved temporal resolution, semiautomatic definition of regions-of-interest including definition of reference regions-of-interest for the detection of background density changes and quality-controlled densitometric parameter analysis. This progress made an application during routine cardiac catheterization feasible. In animal validation studies this improved X-ray densitometric approach for evaluation of local myocardial perfusion was validated versus colour-coded microsphere techniques. The time parameter "rise time", defined as the time from the start of local contrast medium induced density change to its maximum revealed a close correlation (r2 = 0.965) to the results of the microsphere technique over a wide range of perfusion. We have applied this technique before and after coronary interventions such as balloon angioplasty and stenting. Results documented an improvement of poststenotic myocardial perfusion reserve immediately after coronary balloon angioplasty and an additional improvement after adjunct coronary stenting. Only after stenting but usually not after coronary balloon angioplasty alone poststenotic myocardial perfusion reserve gained the intraindividual reference level, measured in a perfusion bed supplied by an epicardial coronary artery without stenoses. These results documented the functional benefit of coronary stenting on poststenotic myocardial perfusion in addition to the well known morphologic benefit with the creation of a larger and more circular conduit.

Absorptiometry, Photon↗
PubMed1997

Contrast echocardiography for assessment of myocardial perfusion.

It has been suggested that the myocardial perfusion can be qualitatively and quantitatively assessed by different ultrasound contrast techniques. It has been reported that the intracoronary or intraaortic administration of the ultrasound contrast agents can be used to visualize perfusion defects or to analyze the coronary flow reserve. The perfusion analysis after intracoronary injection of ultrasound contrast agents seems to be established, but there are a lot of open questions. A topographic (qualitative) perfusion analysis with visualization of perfusion defects and perfusion areas or analysis of collaterals has been demonstrated. A quantitative analysis of myocardial blood flow has been described but the existing studies are inconsistent. It is not known which parameters of the contrast wash-out curves should be used for perfusion analysis and if the Stewart-Hamilton curve analysis can be transferred to all ultrasound contrast agents as a model for quantitative myocardial blood flow assessment. The development of the transpulmonary contrast agents for echocardiographic evaluation of left ventricular cavity has the impact for myocardial perfusion imaging. The increase of myocardial intensity does not mean that a qualitative or quantitative perfusion analysis can be clinically used. In this field we have to differentiate between the possibilities of qualitative discrimination of perfusion defects and quantitative perfusion (myocardial blood flow) analysis. The different scanning conditions, the poor transthoracic ultrasound window and insufficient enhancement of the myocardial intensity make it problematic to quantify the myocardial perfusion. At the moment myocardial intensity will be increased after intravenous injection of transpulmonary contrast agents, but the value for perfusion analysis has not been shown. New ultrasound technologies such as second harmonic imaging, power-mode and raw data analysis have to show the clinical importance of these techniques for perfusion analysis in daily clinical routine. The open questions of the perfusion analysis by contrast echocardiography will be discussed in this review article.

Contrast Media↗
PubMed1997

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischaemia 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, dysfunctional myocardium but also to distinguish between hibernating and stunned myocardium. The 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 is severe, involves large parts of the left ventricle and thus impairs global left ventricular function, it can be reversed with inotropic agents and procedures. In the experimental setting, anti-oxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischaemia.

Animals↗
PubMed1997

Myocardial, skeletal muscle, and renal blood flow during exercise in conscious dogs with heart failure.

The present study characterizes the hemodynamic and neurohumoral responses to moderate treadmill exercise in conscious dogs with pacing-induced heart failure. Seven dogs were instrumented with a left ventricular micromanometer, ultrasonic crystals for the measurement of systolic wall thickening, left atrial and aortic catheters for the injection of colored microspheres and reference withdrawal, respectively, and ventricular pacing leads with a subcutaneous pacemaker. Dogs were run on a treadmill at a speed of 5 km/h. After control studies, heart failure was induced by rapid left ventricular pacing at 250 beats/min for (mean +/- SD) 23 +/- 6 days. In the control state, cardiac output was increased from 4.5 +/- 1.5 to 7.9 +/- 1.4 l/min (P < 0.05 vs. rest). With heart failure, cardiac output was decreased to 2.5 +/- 0.5 l/min at rest (P < 0.05 vs. control state) and was only 3.0 +/- 0.3 l/min during exercise (P < 0.05 vs. control state; not significant vs. rest). Myocardial and, more so, skeletal muscle blood flows at rest were reduced in heart failure; their increases with exercise were attenuated. An increase in renal blood flow during exercise in the control state was no longer seen in heart failure. Increases in plasma catecholamines and lactate during exercise were more pronounced in heart failure. In conclusion, in heart failure, the increase in cardiac output during exercise was largely attenuated. Increased catecholamine levels may have contributed to splanchnic vasoconstriction and preferential distribution of cardiac output into the working skeletal muscle.

Animals↗
PubMed1997

Dihydropyridine calcium antagonists: beneficial or adverse effects in the setting of myocardial ischaemia/reperfusion?

Dihydropyridine (DHP) calcium antagonists are established drugs in the management of hypertension and chronic stable angina. However, recently a dose-related increase in the mortality of patients with coronary artery disease with nifedipine has been suggested. The conclusions of this study were seriously contradicted. Therefore, in our laboratory, the effect of the DHP calcium antagonist nisoldipine on ischaemic myocardial blood flow and function, infarct size, and the functional recovery of reversibly injured, reperfused myocardium was once more investigated in controlled in vivo models. In anaesthetized dogs, in the presence of a severe coronary artery stenosis, intravenous nisoldipine decreased poststenotic subendocardial blood flow and contractile function when arterial pressure was decreased. In contrast, when hypotension was prevented by inflation of an intra-aortic balloon, no aggravation of myocardial ischaemia was seen. During exercise, when aortic pressure is raised by catecholamines, nisoldipine may therefore not exert a pro-ischaemic effect, but may rather improve regional myocardial blood flow and function in the ischaemic region. As has been shown for nifedipine, the functional antagonism of alpha-adrenergic coronary vasomotor tone contributes to the improvement of myocardial blood flow and function of the ischaemic region, in particular during exercise. In anaesthetized pigs, intracoronary administration of nisoldipine prior to a 90-min low-flow ischaemia tended to decrease infarct size. Infarct size resulting from prolonged and severe myocardial ischaemia is reduced by one or more preceding short episodes of ischaemia and reperfusion, a phenomenon called ischaemic preconditioning. A transient exposure to exogenous calcium has been shown to mimic ischaemic preconditioning. Thus, a blockade of calcium channels may interfere with this reduction of infarct size. However, in anaesthetized pigs, nisoldipine did not prevent the reduction of infarct size by ischaemic preconditioning. Reperfused myocardium after short periods of myocardial ischaemia is characterized by a reversible, prolonged depression of myocardial function, a phenomenon called myocardial stunning. In anaesthetized dogs, pre-ischaemic intravenous administration of nisoldipine improved the functional recovery of stunned myocardium following a 15-min complete occlusion of the left circumflex coronary artery. Since myocardial blood flow during myocardial ischaemia and reperfusion was not altered and afterload was kept constant by an intra-aortic balloon, the beneficial effect of nisoldipine appears to be related to an attenuated calcium overload during early myocardial ischaemia. In conclusion, pro-ischaemic effects of calcium antagonists can be avoided when the dosage or mode of administration are adjusted to prevent significant decreases in arterial pressure. Patients in such a way under treatment with calcium antagonists will experience an increase in exercise tolerance and also a better recovery of contractile function after the termination of ischaemia.

Animals↗
PubMed1997

Cardioprotection by ACE inhibitors in myocardial ischaemia/reperfusion. The importance of bradykinin.

Myocardial ischaemia, when severe and sustained for more than 40 minutes, results in irreversible damage, i.e. myocardial infarction. However, with early reperfusion, damage is reversible. Complete recovery of contractile function requires some time, despite fully or almost fully restored blood flow. This phenomenon has been termed myocardial stunning. There is experimental evidence showing that angiotensin converting enzyme (ACE) inhibitors limit the development of infarct size, reduce the incidence of ischaemic and reperfusion arrhythmias, and enhance the recovery of contractile function of stunned myocardium. These cardioprotective effects of ACE inhibitors are mediated by an attenuated degradation of bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Pathophysiology of ischemic myocardial dysfunction].

Myocardial ischemia has been viewed traditionally as an imbalance between energy supply and demand. Within the first few seconds following an acute reduction of myocardial blood flow, energy demand of the hypoperfused myocardium clearly exceeds the reduced energy supply. However, this imbalance is an inherently unstable condition since ischemia induces mechanisms which reduce contractile function and thus energy demand. The mechanisms responsible for the rapid reduction in contractile function during acute myocardial ischemia remain unclear. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow, i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, though at the expense of a renewed worsening of the metabolic status. This situation of increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, the development of short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present; a significant involvement of adenosine and of activation of ATP-dependent potassium channels has been excluded.

Cardiotonic Agents↗
PubMed1996

Calcium responsiveness in regional myocardial short-term hibernation and stunning in the in situ porcine heart. Inotropic responses to postextrasystolic potentiation and intracoronary calcium.

BACKGROUND: We tested the hypothesis that decreased calcium responsiveness is responsible for the reduction in contractile function in regional hibernating and stunned myocardium in situ. METHODS AND RESULTS: In 19 anesthetized swine, the left anterior descending coronary artery flow was reduced to decrease anterior myocardial work index (sonomicrometry) by approximately 60%. During 90 minutes of hypoperfusion, creatine phosphate recovered (as determined by biopsy specimens and bioluminescence) and no necrosis developed (as determined by staining with triphenyl tetrazolium chloride). In 10 swine, changes in the intracellular calcium concentration were induced by systematic variation of the postextrasystolic time interval at a constant prematurity. In 9 additional swine, a graded IC calcium infusion was performed. Under control conditions, anterior myocardial work increased with a fully compensated postextrasystolic time interval from 380+/-93 (mean+/-SD) to 523+/-98 mm Hg . mm. IC calcium infusion increased anterior myocardial work under control conditions from 356+/-85 to a maximum of 428+/-93 mm Hg . mm. Although the maximal responses were decreased during postextrasystolic potentiation (222+/-68 versus 523+/-98 mm Hg . mm) and calcium infusion (176+/-32 versus 428+/-93 mm Hg . mm) after 90 minutes of ischemia, the relationships between increases in anterior myocardial work and, respectively, postextrasystolic time interval and IC calcium were not different. The same was true after 30 minutes of reperfusion. CONCLUSIONS: Both regional hibernating myocardium and stunned myocardium in situ are characterized by a decrease in overall myocardial calcium responsiveness; however, there appears to be no significant myocardial desensitization to calcium.

Animals↗
PubMed1996

Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat.

The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely used to prevent platelet aggregation. The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet aggregation. The dogs were then anesthetized thoracotomized and subjected to 15 min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT, sonomicrometry) of these groups were measured and data compared to placebo-controls (group III, n = 11) and dogs receiving only ramiprilat before LCx-occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic balloon, and heart rate did not change. PMBF was not different between the five groups. Under control conditions and during myocardial ischemia PWT was also not different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups III and V). The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is not prevented by aspirin in dosages which are nevertheless sufficient to inhibit platelet aggregation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

No attenuation of ischaemic preconditioning by the calcium antagonist nisoldipine.

In anaesthetized dogs, intracoronary infusion of calcium prior to a prolonged ischaemic period reduced infarct size, thereby mimicking the protective effects of ischaemic preconditioning and suggesting that an increase in the intracellular calcium concentration might be an important mechanism underlying this phenomenon. The aim was to determine whether pretreatment with the calcium antagonist nisoldipine attenuates the reduction in infarct size achieved by ischaemic preconditioning. In 10 enflurane-anaesthetized pigs serving as controls (group 1), the inflow into the cannulated left anterior descending coronary artery was reduced (low-flow ischaemia) to achieve a 90% reduction in an anterior myocardial work index (sonomicrometry) for 90 min. In 11 pigs (group 2), a cycle of 10 min of low-flow ischaemia and 15 min of reperfusion (preconditioning) preceded the prolonged ischaemia. In groups 3 (n = 9) and 4 (n = 7), nisoldipine was administered by intravenous infusion (500 ng/kg/min) starting 40 min prior to and then throughout a protocol identical to that of groups 1 and 2, respectively. Subendocardial blood flow was measured with radiolabelled microspheres. Infarct size (% area at risk) was determined by triphenyltetrazolium staining in all pigs after 120 min of reperfusion. Subendocardial blood flow in the area at risk was similar in all four groups (group 1: 0.09 +/- 0.04 ml/min/g; group 2: 0.05 +/- 0.03; group 3: 0.09 +/- 0.03; group 4: 0.07 +/- 0.03). Group 2 had reduced infarct size when compared with group 1 (2.6 +/- 3.0% v 12.4 +/- 8.7%, P = 0.004), and there was a trend for a reduction in infarct size following nisoldipine treatment (group 3: 10.2 +/- 7.1%, group 4: 1.6 +/- 2.8%, P = 0.01). Thus administration of nisoldipine in pigs tended to decrease infarct size, and did not abolish the cardioprotection afforded by ischaemic preconditioning.

Analysis of Variance↗
PubMed1996

Hibernating myocardium: a review.

Within a few seconds after a sudden reduction of coronary blood flow regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function during acute myocardial ischemia remain unclear, but may involve a rise in inorganic phosphate. When severe ischemia, such as resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, the development of short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present; a significant involvement of adenosine and of activation of ATP-dependent potassium channels has been excluded. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction which is fully reversible upon reperfusion. Clinical syndromes consistent with the existence of myocardial hibernation include unstable and stable angina, acute myocardial infarction and left ventricular dysfunction and/or congestive heart failure. In long-term hibernating myocardium morphological alterations occur; the myofibrils are reduced in number and disorganized and myocardial glycogen content as well as the extracellular collagen network are increased. Thus, despite the fact that the myocardium remains viable during persistent ischemia and contractile dysfunction is reversible upon reperfusion, there are severe morphological alterations. Understandably, full functional recovery following reperfusion might therefore require weeks or even months.

Animals↗