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Biomedical subjects

G Heusch

Publications and source records attributed to G Heusch.

At least 217 records · Page 12Linked to original sources
PubMed1984

[Significance of the sympathetic nervous system for the coronary circulation].

The activation of sympathetic nerves plays a significant role in the initiation of acute myocardial ischemia. In this review the effects of sympathetic nerves on coronary blood flow are summarized. Under physiological conditions the increase in myocardial performance during sympathetic activation is accompanied by metabolic coronary vasodilation. The resulting increase in coronary blood flow is limited by about 30% by alpha-adrenergic coronary constriction. Extravascular compression and beta-adrenergic coronary dilation are of minor importance during sympathetic activation. With exhausted coronary reserve distal to severe coronary stenoses metabolic vasodilation during sympathetic activation is not possible any more; an alpha 2-adrenoceptor-mediated coronary vasoconstriction now predominates. This coronary constriction induces ischemia of the post-stenotic myocardium. The alpha-antagonists Phentolamine and Rauwolscine as well as the calcium-antagonist Nifedipine prevent poststenotic coronary constriction and myocardial ischemia. Also in the genesis of coronary arterial spasm the sympathetic nervous system may play an important role; the constriction of epicardial coronary arteries is mediated by alpha 1-adrenoceptors. The sympathetic nervous system is not only involved in the initiation of myocardial ischemia, but is also activated by ischemia. This feedback-activation of sympathetic nerves leads to an aggravation of myocardial ischemia.

Coronary Circulation↗
PubMed1983

Interaction of methoxamine with compensatory vasodilation distal to coronary stenoses.

The interaction of alpha 1-receptor mediated vasoconstriction with the compensatory vasodilation distal to coronary stenoses was examined in 9 open-chest dogs. Stenoses on proximal circumflex artery were produced by a circumferential wire snare; an intermediate stenosis was defined by reduction of the reactive hyperemia repayment to 70%, a critical stenosis by prevention of any repayment following a 15-s occlusion. Methoxamine (Vasoxine), 500 micrograms, was infused via a small catheter distal to the stenosis under a constant coronary perfusion pressure of 80 mmHg and a constant heart rate of 160 bpm. The vasoconstrictive response to methoxamine correlated with the degree of reactive hyperemia repayment after 15 s occlusion (r = 0.74) and the preexisting level of poststenotic resistance (r = 0.62). At increasing peripheral coronary pressure distal to the stenosis the resistance of the stenosis was reduced (r = -0.84). Thus, alpha 1-adrenergic vasoconstriction is less marked with increasing compensatory vasodilation distal to coronary stenosis. The severity of the stenosis is reduced at increased intraluminal pressure, probably by distention of its luminal area. Methoxamine might induce a redistribution of coronary blood flow towards ischemic regions and reduce ischemic injury.

Animals↗
PubMed1983

Effects of cardiac contraction on segmental coronary resistances and collateral perfusion.

This study examined the reactions of coronary arteries and microvessels to changes in left ventricular pressure, as well as their significance for collateral circulation. Collateral perfusion pressure was measured as peripheral coronary pressure of an occluded coronary artery after embolisation of its terminal vascular bed with 20 micron microspheres in 9 anesthetized dogs. With measurement of collateral perfusion pressure it was then possible to determine the segmental coronary resistances of the coronary arteries and the microvasculature. Left ventricular pressure was increased by aortic clamping during autoregulation and after maximal pharmacological dilation of the coronary circulation. During autoregulation, the increase in left ventricular pressure induced a resistance decrease mainly in the postcollateral microvessels. With maximal vasodilation, the increase in left ventricular pressure induced a resistance increase mainly in the postcollateral microvessels. Finally with ventricular fibrillation, the resistance of the postcollateral microvasculature was markedly decreased. We conclude that both metabolic regulation of coronary blood flow and extravascular compression of coronary circulation by cardiac contraction act predominantly on postcollateral microvessels. Coronary collateral circulation may be impaired at increased left ventricular pressure.

Animals↗
PubMed1981

[Problems of adaptation in hypertension research (author's transl)].

Emotional stress testing was performed twice in 12 normotensive and 12 hypertensive patients. When compared with normotensive persons, hypertensive patients had a clearly greater adaptation of blood pressure response in second stress test. This effect was so pronounced that differences between normotensive and hypertensive persons observed in the first test disappeared. Because of this pronounced adaptation effect, demonstrated until now only for emotional stress, intraindividual comparison does not seem a method of choice in the evaluation of antihypertensive effects by stress situations. Specific influence of antihypertensive drugs on emotional blood pressure reactions can only be demonstrated in the inter-individual comparison with another antihypertensive drug. First comparison between both groups should only be done after establishing a therapeutic effect on resting blood pressure.

Adaptation, Physiological↗
PubMedDate not supplied

Characterization of the inotropic and arrhythmogenic action of the sodium channel activator BDF 9148: a comparison to its S-enantiomer BDF 9196, to its congener DPI 201-106, to norepinephrine, and to ouabain.

Positive inotropic substances which enhance the myocardial cAMP level or inhibit the Na+/K(+)-ATPase are known for their proarrhythmic side-effects. This study was performed to investigate the inotropic and arrhythmogenic action of the Na(+)-channel activator BDF 9148 (racemate) in comparison to its S-enantiomer BDF 9196, its congener DPI 201-106 (racemate), to norepinephrine, and to ouabain. In 30 open-chest dogs, the effects of these substances on the first derivative of left ventricular pressure (dP/dt, Millar-tip catheter) and anterior systolic wall thickening (AWT, sonomicrometry) were studied. Concomitantly, myocardial excitability, conduction times, and refractory period were assessed with a transmural, three-dimensional, 16-electrode array in the anterior wall. For the study of the Na(+)-channel activators, alpha- and beta-adrenergic and muscarinic receptors were blocked. A first set of measurements was performed during normoperfusion with administration of BDF 9148 (1 mg/kg, n = 8), BDF 9196 (0.5 mg/kg, n = 8), and DPI 201-106 (1 mg/kg, n = 8), respectively. A second set of measurements was performed with administration of the threefold dosage of either substance. With a severe stenosis on the left anterior descending coronary artery, a final set of measurements was performed, again using the higher dosage of either substance. For the study of norepinephrine (0.5 micrograms/kg/min i.v., n = 6) and ouabain (40 micrograms/kg i.v., n = 4), measurements were performed during normoperfusion in additional animals. Under normal conditions, either Na(+)-channel activator induced increases in dP/dtmax (lower dosage: 45-84%, higher dosage: by 93-117%) and AWT (lower dosage: by 24-37%, higher dosage: by 19-56%). Under ischemic conditions, either drug increased dP/dtmax by 60-98% and AWT by 45-102%. Excitability, conduction times, and refractory period did not change significantly in response to the Na(+)-channel activators, neither under normal nor under ischemic conditions. There was no significant difference in the incidence of spontaneous ventricular extrasystoles before and after administration of either Na(+)-channel activator. In contrast, an equi-inotropic dosage of norepinephrine (increases in dP/dtmax by 148% and AWT by 42%) increased excitability, decreased conduction times and refractory period, and increased the incidence of spontaneous ventricular extrasystoles. Ouabain induced only a moderate increase in dP/dtmax by 56% and AWT by 24%, but elicited sustained and complex ventricular arrhythmias. Excitability was markedly increased, whereas conduction times and refractory period changed only little.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMedDate not supplied

Neuronal control of coronary blood flow.

Controversies on acetylcholine-induced increases or decreases in coronary blood flow arise from obvious species differences, the role of endothelium in mediating vascular smooth muscle responses, and the marked negative chronotropic and inotropic effects of acetylcholine. In man, there appears to be a predominant dilation of intact epicardial coronary arteries and a constriction of artherosclerotic segments. However, at present there is no evidence for a vagal initiation of myocardial ischemia. Coronary vascular beta-adrenergic receptors mediate dilation, but appear to be functionally insignificant during sympathetic activation. The beta-adrenergic mechanism contributing to myocardial ischemia are indirect, mediated by a tachycardia-related redistribution of blood flow away from the ischemic myocardium. alpha-Adrenergic receptors mediating epicardial coronary artery constriction in experimental studies appear not to be responsible for the initiation of ischemia in patients with angina at rest. However, alpha-adrenergic constriction of coronary resistance vessels resulting in the precipitation of post-stenotic myocardial ischemia was demonstrated in experimental studies and recently confirmed in patients with effort angina. Non-adrenergic, non-cholinergic neurotransmitters exist; however, their role in regulating coronary blood flow remains entirely unclear.

Acetylcholine↗
PubMedDate not supplied

Alpha 1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs.

The effect of selective alpha 1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after beta-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to block potential prejunctional effects recently recognized with alpha-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of regional systolic wall thickening of the post-stenotic myocardium from a resting value of 21.8% to 7.0%. Blood flow to the ischemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microspheres). Prazosin (80 micrograms/kg i.v.) was administered during continued running, and angiotensin II was simultaneously infused to prevent the decrease in systemic arterial pressure caused by prazosin. During the subsequent steady state, with arterial pressure matched to the pre-prazosin level, regional subendocardial blood flow improved to 0.60 ml/min/g and systolic wall thickening in the post-stenotic region increased modestly to 10.2%. No changes in blood flow to the outer portion of the post-stenotic region or to the remote control region were seen, and prazosin caused no effect on regional function in the control area, indicating effective blockade of prejunctional effects of prazosin (demonstrated in pilot studies). The finding that blockade of alpha 1-adrenoceptors resulted in improved ischemic zone subendocardial blood flow and contractile function are consistent with alpha 1-adrenoceptor-mediated reduction of blood flow to the ischemic subendocardium during exercise-induced ischemia in dogs with beta-blockade.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Three-dimensional analysis of regional mechanical function, blood flow and electrophysiological parameters during early myocardial ischemia in dogs.

Ventricular arrhythmias are primarily responsible for sudden cardiac death early after the onset of acute myocardial ischemia. We designed an experimental model to simultaneously characterize regional myocardial function, myocardial blood flow, and electrophysiological parameters, and to determine predisposing factors for the development of early ventricular arrhythmias (EVA). The left circumflex coronary artery was occluded in six anesthetized (n = 2 piritramide/N2O, n = 4 chloralose/urethane) mongrel dogs. Systolic wall thickening (%WT) in a control zone and in the central ischemic zone was measured with sonomicrometry and regional myocardial blood flow (RMBF) with colored microspheres. Excitability and relative refractory period at the stimulus electrode and conduction times to all other electrodes were determined with a three-dimensional transmural multi(16)-electrode assay using a computer algorithm. In three of six dogs spontaneous EVA occurred 4 to 6 min after coronary occlusion, degenerating to ventricular fibrillation in two of these dogs. The three dogs developing EVA were not distinguished from those not developing EVA, neither by the kind of anesthesia nor by ischemic % WT (-6.6 +/- 3.8 [SD] vs -7.8 +/- 1.6, ns). Also, dogs with and without EVA did not differ significantly in excitability and relative refractory period. In contrast, dogs with EVA were characterized by a greater mass of severely ischemic myocardium, i.e., exhibiting a RMBF reduction to less than 0.1 ml/(min.g) (18 +/- 3 g vs 7 +/- 4 g, p less than 0.05), and by an increase in subendocardial conduction times of greater than 100% above the respective pre-ischemic values (120 +/- 18% vs 66 +/- 9%, p less than 0.05). Dogs with and without EVA were not as clearly distinguished by the increases in subepicardial (81 +/- 22% vs 46 +/- 15%, ns) and transmural (98 +/- 31% vs 67 +/- 14%, ns) conduction times. The development of EVA is associated with a greater mass of severely ischemic myocardium and a greater increase in subendocardial conduction times.

Animals↗
PubMedDate not supplied

Recruitment of inotropic reserve in "stunned" myocardium by the cardiotonic agent AR-L 57.

Contractile dysfunction of reversibly injured, reperfused myocardium can be enhanced by inotropic interventions. A decrease in the Ca-sensitivity of contractile proteins with slow recovery during reperfusion has been suggested as a potential mechanism underlying this postischemic dysfunction. We therefore tested the effects of the cardiotonic agent AR-L 57 (1 mg/kg i.v.) in six anesthetized, vagotomized dogs during constant atrial pacing at 192 +/- 6 beats/min. Before ischemia, AR-L 57 increased left ventricular pressure from 131 +/- 22 to 138 +/- 21 mm Hg and maximum dP/dt from 3,022 +/- 1,427 to 4,337 +/- 2,608 mm Hg/s. Mean systolic thickening velocity of the posterior myocardium was increased from 8.9 +/- 1.1 to 11.7 +/- 1.1 mm/s. After release of a 15 min LCX-occlusion which caused complete regional akinesia, baseline function in the posterior myocardium was severely depressed and only gradually returned towards control values over 8 h of reperfusion. AR-L 57 increased systolic thickening velocity at 10 min, 4 and 8 h reperfusion to a similar extent as before ischemia. With reference to a purported Ca-sensitizing mechanism underlying the positive inotropic action of AR-L 57, our data suggest no change in the Ca-sensitivity of reperfused myocardium.

Animals↗
PubMedDate not supplied

An easy and quick implantation procedure for the measurement of myocardial wall thickness using sonomicrometry.

Ultrasonic techniques for the measurement of ventricular dimensions are widely used in acute and chronic experiments. Implantation of ultrasonic crystals is associated with reversible and irreversible myocardial damage which might limit the interpretation of the obtained results, in particular during acute experiments. We therefore developed a sonomicrometric device which can be easily and quickly implanted, and thus reduces the reversible myocardial damage induced by prolonged surgical implantation.

Animals↗