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Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

At least 199 records · Page 11Linked to original sources
PubMed1987

Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs.

Postreperfusion regional myocardial dysfunction may be associated with depletion of high energy phosphate compounds during ischemia and with their relatively slow repletion during reperfusion. However, few studies have correlated relatively rapid changes in regional myocardial function (sonomicrometers) and blood flow (microspheres) with high energy phosphate concentrations measured using phosphorus-31 nuclear magnetic resonance spectroscopy in intact large animal models of regional myocardial ischemia. The left anterior descending coronary artery of mongrel dogs was abruptly occluded for 17.1 +/- 1.9 minutes and then completely released; measurements were made for an additional 22 minutes. Transmural blood flow decreased from 1.07 +/- 0.25 to 0.25 +/- 0.10 ml/(min X g) and holosystolic expansion was observed in all dogs (segmental systolic shortening decreased from 9.3 +/- 3.7 to -6.3 +/- 6.0%). Phosphocreatine (PCr) measured during 4.4 minute sampling intervals decreased to steady state within the first sampling period after occlusion and was 45.9 +/- 17.0% of control at the end of the occlusion, whereas beta-adenosine triphosphate (beta-ATP) reached its lowest level early after reperfusion (72.7 +/- 13.3% of control). The ratio of PCr to inorganic phosphate (Pi) decreased during the occlusion (3.34 +/- 0.75 versus 1.01 +/- 0.61) but returned to control level early during reperfusion. The ratio of PCr to beta-ATP also decreased during coronary occlusion (2.16 +/- 0.39 versus 1.29 +/- 0.39) but did not return to control level during reperfusion. Significant correlations were observed between the intensity of ischemia (reduced blood flow) and reductions in regional contractile function, PCr, beta-ATP, myocardial pH and the increase in Pi during the coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Role of heart rate reduction in the treatment of exercise-induced myocardial ischaemia.

The role of bradycardia in reducing exercise-induced ischaemia and wall dysfunction was examined in dogs with single vessel chronic coronary artery stenosis created using an ameroid constrictor. Treadmill exercise produced significant regional myocardial ischaemia (blood flow measured using microspheres) and contractile dysfunction (systolic wall thickening measured with sonomicrometers). Dogs were initially studied during a control run before and during a second identical run after administration of the cardioselective beta-adrenergic blocker atenolol, which improved regional ischaemic function from 4.4 +/- 3.7% to 8.5 +/- 2.8% and subendocardial perfusion from 0.43 +/- 0.23 to 0.55 +/- 0.29 ml min-1 g-1. In another group of dogs during a run with atenolol, the heart rate was paced to match the rate observed in the control run. During the atenolol run with pacing, all beneficial effects of atenolol observed at the reduced exercise heart rate were lost. A third group of dogs received the bradycardic agent UL-FS 49 (1.0 mg kg-1, i.v.) prior to exercise. UL-FS 49 produced a heart rate reduction during exercise from 230 +/- 19 to 139 +/- 10 beats min-1; this was associated with an increase in systolic wall thickening from 9.3 +/- 5.0% (during the control run) to 21.5 +/- 8.4%, thereby eliminating the exercise-induced contractile dysfunction. Transmural myocardial blood flow per beat to the poststenotic myocardium was improved significantly from 4.8 X 10(-3) +/- 1.9 X 10(-3) ml beat-1 to 9.8 X 10(-3) +/- 1.7 X 10(-3). Atrial pacing to match heart rate to the control exercise rate during the UL-FS 49 run did not eliminate all of the improvement in systolic wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Quinidine attenuates sympathetically induced poststenotic myocardial ischemia.

Beside its antiarrhythmic properties, which in particular are used for the treatment of atrial fibrillation, quinidine is known to have alpha-adrenoceptor blocking properties. On the other hand, atrial fibrillation is reported to cause activation of the sympathetic nervous system which, in turn, reduces coronary blood flow when the coronary reserve is already compromised. Therefore, we tested the effect of quinidine (3 mg/kg i.v.) on the coronary vasculature during electrical stimulation of cardiac sympathetic nerves in the presence and absence of a stenosis on the left circumflex coronary artery. In 7 anesthetized dogs the end-diastolic distal coronary resistance during cardiac sympathetic nerve stimulation in the presence of a severe stenosis on the left circumflex coronary artery increased by 18% before, and decreased by 17% after administration of quinidine. We conclude that quinidine inhibits the vasoconstriction of poststenotic coronary arteries during cardiac sympathetic nerve stimulation and thus might prevent a poststenotic stress-induced myocardial ischemia.

Adrenergic alpha-Antagonists↗
PubMed1987

Contractile responses to sympathetic activation after coronary instrumentation.

The consequences of acute coronary dissection and chronic coronary instrumentation on contractile responses to sympathetic activation were examined in dogs. Stimulation of the left ventrolateral cervical cardiac nerve in seven anesthetized dogs after acute dissection of the left circumflex coronary artery (CX) did not change the increase in systolic shortening velocity. After acute dissection of the left anterior descending coronary artery (LAD), nerve stimulation increased shortening velocity of the posterior wall in all dogs but enhanced that of the anterior wall in only five dogs. In six conscious dogs with chronic instrumentation of the CX, reflex sympathetic activation induced by occlusion of the inferior vena cava comparably increased thickening velocities of both the anterior wall and posterior walls both at 1 and 3 wk after instrumentation. In six other dogs with chronic instrumentation of the LAD, responses to caval occlusion were nonuniform and correlated to the morphological degree of sympathetic denervation. Therefore, acute dissection and chronic instrumentation of the LAD may produce sympathetic denervation but do not cause functionally significant sympathetic denervation of the CX region.

Animals↗
PubMed1987

Effects of left circumflex Ameroid constrictor placement on adrenergic innervation of myocardium.

We evaluated the adrenergic innervation of the swine and canine myocardium after placement of an Ameroid constrictor around the left circumflex coronary artery (LCX). Fluorescent histochemistry was used to identify adrenergic nerve terminals in the myocardium and coronary vasculature. Ameroid occlusion of the proximal LCX in 10 pigs for 3 wk resulted in 6 +/- 1% infarction as well as myocardial ischemia in the left circumflex region of pigs studied during exercise. However, placement of the Ameroid constrictor did not significantly alter the surface density of the nerve terminals in the LCX region of myocardium when compared with innervation of control hearts. Histological examination of the coronary arterial adrenergic innervation in Ameroid-occluded pigs revealed that coronary vessels in the circumflex region of the heart were innervated. Similarly, in seven LCX Ameroid-occluded dogs, no significant decrease in adrenergic innervation of the LCX region of myocardium was observed when compared with control dogs. In contrast LCX Ameroid-occluded pigs demonstrated significant (P less than 0.01) denervation of the left anterior descending (LAD) region of myocardium when compared with control animals. The close proximity of adrenergic nerve bundles in the proximal LAD region indicates that denervation of the myocardium supplied by the LAD may result from the dissection and/or fibrosis associated with placement of the Ameroid constrictor on the proximal LCX. Our results suggest that placement of an Ameroid constrictor on the proximal LCX does not significantly alter the adrenergic innervation of the LCX-perfused myocardium or its associated coronary vasculature. However, denervation of LAD-perfused myocardium and its vasculature may result.

Adrenergic Fibers↗
PubMed1987

Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.

There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.

Animals↗
PubMed1987

Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis.

We have previously demonstrated that the beneficial effect of cardioselective beta-blockade on exercise-induced ischemia is due entirely to negative chronotropism. Therefore we studied the effect of a new bradycardiac agent (UL-FS 49) in 10 dogs with chronic coronary artery stenosis produced by an ameroid constrictor. Regional myocardial function (sonomicrometers, wall thickness) and blood flow (microspheres) were measured during a control treadmill exercise bout and an identical run 3 hr later after the administration of UL-FS 49 (1.0 mg/kg iv). In the control run, heart rate increased from 114 +/- 20 to 230 +/- 19 beats/min and systolic wall thickening (%WT) in the poststenotic myocardium decreased from 23.3 +/- 5.2% at rest to 9.3 +/- 5.0%, a 60% reduction. Subendocardial blood flow in the ischemic area decreased from 1.04 +/- 0.30 to 0.55 +/- 0.40 ml/min/g, blood flow per beat decreased from 9.1 X 10(-3) to 2.5 X 10(-3) ml/g, and mean transmural flow failed to increase (1.06 +/- 0.30 vs 1.08 +/- 0.39 ml/min/g). During exercise with UL-FS 49, heart rate increased from 89 +/- 10 to only 139 +/- 10 beats/min. End-diastolic left ventricular pressure was increased compared with that during the control run (35.7 +/- 3.0 vs 28.9 +/- 5.5 mm Hg) but left ventricular peak systolic pressure and dP/dt were unchanged. %WT in the ischemic zone did not change significantly during exercise with UL-FS 49 (23.3 +/- 7.9% at rest, 21.5 +/- 8.4% during the run), and in the nonischemic zone it increased to the same extent as during the control run.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mechanism of beneficial effect of beta-adrenergic blockade on exercise-induced myocardial ischemia in conscious dogs.

We examined the importance of decreased heart rate in the beneficial effect of beta-adrenergic blockade on exercise-induced regional myocardial ischemia and contractile dysfunction in conscious dogs with single vessel coronary stenosis (ameroid constrictor). Studies were performed during control treadmill exercise, which produced regional myocardial ischemia (blood flow measured with microspheres) and wall dysfunction (measured using sonomicrometers). A second run was performed after the administration of atenolol (0.3-1.0 mg/kg i.v.), and the reduced heart rate caused by atenolol during early steady-state running was then prevented by atrial pacing during the latter portion of the run. Atenolol reduced the exercise heart rate from 217 +/- 25 beats per minute (SD, n = 9) to 166 +/- 15, and ischemic zone wall thickening during systole improved from 27 +/- 22% of the resting value in the control run to 50 +/- 25% of the resting value in the atenolol run (p less than 0.01). Atrial pacing then increased heart rate to 217 +/- 23 beats per minute, and regional wall thickening deteriorated to 15 +/- 25% of the resting value. Regional subendocardial blood flow in the ischemic zone during atrial pacing with atenolol was slightly less than that observed in the control run, in both ischemic and control zones, indicating no remaining beneficial effect of atenolol when heart rate reduction was eliminated. We conclude that the only significant mechanism for the improvement in exercise-induced ischemia and wall motion produced by atenolol is a reduction in the exercise heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evidence against the adenosine-catecholamine antagonism in the canine heart in situ.

Adenosine has been reported to attenuate the positive inotropic effects of catecholamines in isolated heart preparations of rodents. These results were not confirmed in anesthetized dogs during intracoronary infusion of isoprenaline. However, these experiments did not establish the effects of adenosine on the inotropic effects of endogenously released catecholamines. Therefore cardiac sympathetic nerve stimulation was performed in 5 anesthetized, vagotomized dogs. The left circumflex coronary artery was perfused at a constant pressure of 130 +/- 4 mmHg. The contractile function of the circumflex-perfused myocardium was analyzed by sonomicrometry. Cardiac sympathetic nerve stimulation at 1, 2, 5, 10 and 20 Hz increased systolic segment shortening in a frequency-dependent manner from 10.9 +/- 2.6 at control to 15.3 +/- 3.4% at 20 Hz. During intracoronary infusion of adenosine (50 micrograms/kg/min) cardiac sympathetic nerve stimulation still increased systolic segment shortening from 9.9 +/- 3.5 at control to 16.3 +/- 4.5% at 20 Hz. The lack of an adenosine-catecholamine antagonism in the present experiments was not due to the sequence of procedures, nor to the marked flow increase induced by adenosine, since systolic segment shortening at rest was reduced during adenosine infusion, and since during intracoronary infusion of papaverine and sodium nitroprusside similar results were obtained. The observation of an adenosine-catecholamine antagonism in rodents should be restricted to this species at present.

Adenosine↗
PubMed1986

Evaluation of acute stress-induced regional myocardial ischemia: comparison of regional contractile and metabolic indices to easily accessible global left ventricular indices.

In clinical studies stress-induced myocardial ischemia in patients with coronary artery disease is used to evaluate the severity of this disease. The discussion on the importance of some parameters measured during this intervention is controversial, other parameters are difficult to obtain. On the basis of an experimental model of stress-induced myocardial ischemia, we tried to find an index that reflects best this cardiac state. We therefore compared in eight anesthetized open-chest dogs control conditions with three other hemodynamic states with increasing imbalance between myocardial oxygen demand and oxygen supply: severe stenosis on circumflex coronary artery, 60 s cardiac sympathetic nerve stimulation (CSNS) with a severe stenosis on circumflex coronary artery, and 60 s complete occlusion of circumflex coronary artery. Using a one-way analysis of variance, we found two significantly changed parameters during the stress-induced ischemia: Regional lactate extraction was turned to production (32 +/- 4 vs. -4 +/- 1%) and the ratio of dP/dtmin to dP/dtmax was decreased (1.13 +/- 0.05 vs. 0.67 +/- 0.05; control vs. CSNS with a severe stenosis on circumflex coronary artery). We conclude that the ratio of dP/dtmin to dP/dtmax is an easily accessible, sensitive, and dynamic index for characterization of an stress-induced myocardial ischemia.

Animals↗
PubMed1986

Sympathetic mechanisms in poststenotic myocardial ischemia.

A coronary stenosis can be compensated by dilation of the poststenotic vascular bed. Activation of cardiac sympathetic nerves can disturb this balance. Experiments in anesthetized, vagotomized dogs revealed that electrical stimulation of cardiac sympathetic nerves as well as reflex sympathetic activation by bilateral carotid occlusion induce vasoconstriction distal to severe coronary stenoses, which were defined by the lack of any postocclusive reactive hyperemia. The poststenotic vasoconstriction is mediated by alpha 2-adrenoceptors and, in concert with the beta-adrenoceptor mediated increase in myocardial oxygen demand, it induces an acute ischemia of the poststenotic myocardium. This ischemia was evidenced by contractile dysfunction, net lactate production, the occurrence of ventricular fibrillation in 10% of dogs, and the development of subendocardial necroses after repetitive sympathetic stimulation. The alpha-antagonist phentolamine, the selective alpha 2-antagonist rauwolscine, and the calcium antagonist nifedipine prevent both poststenotic vasoconstriction and ischemia, whereas the beta-antagonist propranolol enhances even poststenotic vasoconstriction, but still prevents ischemia. Poststenotic ischemia can thus result from sympathetic activation but, in turn, also activates cardiac sympathetic nerves by a spinal reflex. This positive feedback provides a basis for a progressive poststenotic vasoconstriction and aggravation of myocardial ischemia. This vicious cycle can be interrupted by rauwolscine and nifedipine, as well as by segmental epidural anesthesia with procaine at segments C6-T7. The poststenotic ischemia induced by sympathoexcitatory reflexes can also be prevented by blocking the sympathoexcitation at the central nervous level by clonidine. Our studies emphasize the role of cardiac sympathetic nerves and alpha 2-mediated poststenotic vasoconstriction in the genesis and aggravation of poststenotic myocardial ischemia.

Animals↗
PubMed1986

Adenosine, dipyridamole and isosorbide dinitrate are ineffective to prevent the sympathetic initiation of poststenotic myocardial ischemia.

An activation of cardiac sympathetic nerves increases coronary vascular resistance distal to severe stenoses and induces ischemia of the dependent myocardium. The selective alpha 2-adrenoceptor antagonist rauwolscine and the calcium antagonist nifedipine prevent both poststenotic vasoconstriction and ischemia. To exclude the possibility that the beneficial action of nifedipine is based on unspecific coronary dilation rather than a functional antagonism against alpha 2-adrenoceptor mediated poststenotic vasoconstriction we now tested coronary dilatory drugs with a different underlying mechanism. The left ventrolateral cervical cardiac sympathetic nerve was stimulated in 12 anesthetized, vagotomized dogs. A severe stenosis of left circumflex coronary artery was defined by the absence of a postocclusive reactive hyperemia. Sympathetic stimulation increased end-diastolic poststenotic resistance from 0.45 +/- 0.10 to 0.83 +/- 0.18 mmHg X min X 100 g/ml and induced a net lactate production of the poststenotic myocardium. Adenosine (50 micrograms/kg X min i.c., n = 5), dipyridamole (0.2 mg/kg i.v., n = 3) and isosorbide-dinitrate (1 mg i.c., n = 4) did not prevent the increase in resistance and the net lactate production. Thus the effectiveness to prevent alpha 2-adrenergic poststenotic coronary constriction appears to be specific for alpha 2-antagonists and calcium antagonists.

Action Potentials↗
PubMed1985

Alpha 2-adrenoceptor-mediated coronary vasoconstriction persists after exhaustion of coronary dilator reserve.

The effect of intracoronary administration of the selective alpha 2-adrenoceptor agonist B-HT 920 on coronary resistance was tested in 14 open-chest dogs before and after exhaustion of coronary dilator reserve. Under both conditions B-HT 920 increased coronary resistance to the same extent: 27 +/- 4% before and 32 +/- 3% after. Administration of B-HT 920 did not affect cardiovascular haemodynamics significantly, although after exhaustion of coronary dilator reserve left ventricular dP/dtmax decreased slightly by 12 +/- 5%. While efferent cardiac sympathetic discharge remained constant during control conditions it increased by 27 +/- 7% when B-HT 920 was administered into a stenotic coronary artery. We conclude that, in contrast to observations made on alpha 1-adrenoceptors, activation of coronary alpha 2-adrenoceptors may have deleterious effects after exhaustion of coronary dilator reserve because these receptors mediate a comparable constriction in well- and under-perfused coronary vessels. Thus they are unlikely to favour a redistribution of coronary blood flow into under-perfused myocardial regions. In addition, this unfavourable effect of B-HT 920 on coronary perfusion after coronary dilator reserve has been exhausted may be further exacerbated by an increase in efferent sympathetic discharge.

Adrenergic alpha-Agonists↗
PubMed1985

Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenoses: feed-back aggravation of myocardial ischemia.

This study tested the hypothesis that the relative ischemia distal to a severe coronary stenosis increases the activity of cardiac sympathetic nerves which in turn results in poststenotic vasoconstriction and an aggravation of ischemia. An acute severe stenosis which reduced coronary blood flow to 50% of control was produced in 23 anesthetized, vagotomized dogs and maintained for 20 min. The activity of postganglionic cardiac sympathetic nerves increased by 23 +/- 4% within 20 min. In parallel, poststenotic coronary resistance increased from 0.48 +/- 0.03 to 0.61 +/- 0.03 mm Hg X min X 100 g/ml resulting in a net lactate production after 15 min. Pretreatment with aspirin (6 mg/kg i.v.; n = 5) was without any influence on these reactions. The selective alpha 2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.; n = 6) and the calcium antagonist nifedipine (10 micrograms/kg i.v.; n = 6) prevented the progressive increase in poststenotic resistance and lactate production, but still permitted an increase in sympathetic activity. Segmental anesthesia of cardiac sympathetic nerves by epidural infiltration of procaine at segments C7-T6 (n = 6) prevented the sympathetic activation, the progressive increase in poststenotic resistance and the resulting myocardial ischemia. Sympathetic activation and a concomitant increase in poststenotic resistance resulting in myocardial ischemia were also found in 6 dogs with intact vagus nerves. These data support the hypothesis of a vicious cycle between poststenotic coronary vasoconstriction and sympathetic activation resulting in severe myocardial ischemia.

Animals↗
PubMed1985

Role of cardiac sympathetic nerves in the genesis of myocardial ischemia distal to coronary stenoses.

This manuscript summarizes the effects of cardiac sympathetic nerve activation on coronary blood flow and myocardial function, metabolism, and morphology distal to stenoses. Whereas cardiac sympathetic nerve activation induces an increase in myocardial function and metabolism accompanied by metabolic coronary dilation under physiological conditions, this response is different in the presence of coronary stenoses. With decreasing coronary hyperemic reserve, distal to an increasing degree of coronary stenosis, the predominant response to sympathetic stimulation is continuously shifted from metabolic dilation to alpha-adrenergic vasoconstriction. With a severe coronary stenosis, both electrical stimulation of cardiac sympathetic nerves and reflex sympathetic activation by carotid occlusion induce poststenotic vasoconstriction and ischemia of the dependent myocardium. Poststenotic vasoconstriction is mediated by vascular alpha 2-adrenoceptors and is prevented by phentolamine, rauwolscine, and nifedipine. Prolonged sympathetic activation even results in patchy subendocardial necroses. There is a vicious cycle between poststenotic vasoconstriction, myocardial ischemia, and cardiac sympathetic nerve activity that results in a progressive perfusion impairment during 20 min severe coronary stenosis.

Animals↗
PubMed1985

Acetylcholine induces constriction of epicardial coronary arteries in anesthetized dogs after removal of endothelium.

The acetylcholine-induced relaxation of isolated coronary arteries is reversed to contraction in the absence of endothelium. The importance of endothelium for the regulation of coronary blood flow remains unclear. We thus tested the effects of acetylcholine on epicardial arteries and on coronary resistance vessels in situ in 8 anesthetized dogs. The left circumflex coronary artery was perfused at constant pressure. Epicardial vasomotion was evaluated by sonomicrometry, the vasomotion of coronary resistance vessels by calculated end-diastolic resistance. Acetylcholine (1 microgram/kg/min i.c.) decreased epicardial resistance by 8.6 +/- 1.6% and end-diastolic resistance by 65.8 +/- 6.3%. The epicardial coronary segment was perfused with distilled water for 65 +/- 5 s to denude it of endothelium. After removal of epicardial endothelium, the decrease in end-diastolic resistance caused by acetylcholine was unchanged (59.6 +/- 1.2%); however, epicardial resistance was increased by 7.7 +/- 1.7%. Application of glyceryl trinitrate (5 micrograms/kg/min i.c.) induced a similar decrease of epicardial resistance before and after removal of endothelium:7.9 +/- 1.4 and 6.2 +/- 1.9%, respectively. We conclude that acetylcholine-induced dilation of epicardial coronary arteries is endothelium-dependent in vivo. However, the constriction of epicardial coronary arteries in the absence of endothelium is insufficient to reduce blood flow and to induce myocardial ischemia.

Acetylcholine↗