Brian D. Guth

Koronare Vasomotion bei Myokardischamie

Im Mittelpunkt der vorliegenden Betrachtung soll die Pathophysiologie der Myokarddurchblutung bei regionaler Myokardischamie stehen. Ohne die Bedeutung der extravasalen Komponente des Koronarwiderstandes, insbesondere fur die Verteilung der Durchblutung im ischamischen Myokard [6, 55, 91], geringzuschatzen, sollen hier in erster Linie die aktiven koronarvasomotorischen Mechanismen betrachtet werden.

Coronary Vasomotor Tone in Myocardial Ischemia

This review is focused on the pathophysiology of myocardial perfusion during regional ischemia. The importance of the extravascular component of coronary resistance, in particular for the distribution of blood flow in ischemic myocardium, should not be underestimated [6, 55, 91]. However, this contribution discusses primarily the active coronary vasomotor mechanisms during myocardial ischemia.

α-Adrenergic Regulation of Myocardial Performance in the Exercising Dog: Evidence for Both Presynaptic α1- and α2-Adrenoceptors

New evidence supporting both presynaptic α1- and α2-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective α1-adrenoceptor blocker prazosin (80μg/kg) or the selective α2-adrenoceptor blocker idazoxan (80μg/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either α-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. β-adrenergic blockade prevented the heart rate and contractile effects of either α1 - or α2-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either α-blocker. Together, these studies provide evidence that both α1- and α2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.

Prevention of α-Adrenergic Coronary Constriction by Calcium-Antagonists

This manuscript reviews the experimental evidence for a functional antagonism of Ca-antagonists against α-adrenoceptor-mediated increases in coronary vasomotor tone. In studies on anesthetized dogs, intravenous nifedipine effectively prevented the α1-adrenoceptor-mediated increase in epicardial coronary resistance, as well as the increase in end-diastolic resistance mediated by both α1- and α2-adrenoceptors during cardiac sympathetic nerve stimulation. Both intracoronary and intravenous administration of nifedipine also prevented the α2-adrenoceptor-mediated increase in coronary resistance distal to severe stenoses, as well as the resulting ischemic dysfunction and net lactate production during cardiac sympathetic nerve stimulation. Felodipine was equally effective as nifedipine in preventing an α2-adrenoceptormediated increase in coronary resistance and the resulting contractile dysfunction distal to severe coronary stenoses. α1 - and α2-Adrenergic coronary constriction also contribute to the severity of myocardial ischemia in conscious dogs during treadmill exercise. Again, nifedipine improved regional myocardial blood flow and attenuated regional contractile dysfunction during exercise-induced ischemia in conscious dogs with a chronic coronary stenosis. This beneficial effect of nifedipine was attributed to a recruitment of coronary dilator reserve and not to a reduction in heart rate or afterload. In conclusion, there is solid experimental evidence for a functional antagonism of Ca-antagonists against α-adrenergic coronary constriction and its contribution to myocardial ischemia.

A Brief History of Angina Pectoris: Change of Concepts and Ideas

The history of angina pectoris may be considered in three developmental periods. The first extended from antiquity into the late middle ages during which numerous descriptions of clinical symptoms appeared that, in retrospect, were likely angina pectoris but at the time were not associated with a disease of the heart. The period from the late middle ages to the early 20th century brought about the correlation between angina pectoris and a pathological state of the coronary vessels. Finally, since the 1930s there has been the development of pathophysiological concepts of angina pectoris which now focus on an impaired relation between the work performed by the heart and the oxygen supply to the heart through the coronary circulation.

Exercise-Induced Myocardial Ischemia: The Role of Heart Rate Reduction in Therapeutic Approach

Rational therapy for exercise-induced myocardial ischemia, as manifested by effort angina pectoris, must be based on a thorough understanding of the disease process and its effects on regional myocardial blood flow and contractile function. The clinician has an ever increasing array of pharmaceuticals available with which to treat the coronary disease patient, including s-adrenergic blockers, calcium channel antagonists, and nitrates. This divergent set of agents has markedly different effects on the coronary vasculature, the myocardial contractile state, and the peripheral circulation, thereby making combined pharmacologic therapy attractive in some situations. However, such complicated therpeutic approaches further emphasize the need to fully appreciate the anatomical, physiological, and pathological mechanisms present in the patient, together with the mode of action of each pharmacologic agent utilized. The purpose of this chapter is to discuss the role of tachycardia in the precipitation of myocardial ischemia, as well as the role of heart rate reduction for the treatment of exercise-induced myocardial ischemia in the context of the underlying pathophysiology.

Belastungsinduzierte Myokardischämie: Die Bedeutung der Herzfrequenzreduktion in der Therapie

Eine rationale Therapie der belastungsinduzierten Myokardischamie und der belastungsinduzierten Angina pectoris mus auf einem Verstandnis des Krankheitsprozesses und seiner Auswirkungen auf die regionale Myokarddurchblutung und kontraktile Funktion beruhen. Dem Kliniker steht ein wachsendes Arsenal von Pharmaka fur die Behandlung Koronarkranker zur Verfugung, im wesentlichen Betablocker, Kalziumantagonisten und Nitrate. Diese unterschiedlichen Pharmaka haben deutlich verschiedene Effekte auf die Koronarzirkulation, den kontraktilen Zustand des Myokards und die periphere Zirkulation. Daher erscheint eine Kombinationstherapie in manchen Situationen attraktiv. Solche komplexen therapeutischen Ansatze machen das Verstandnis der anatomischen, physiologischen und pathologischen Mechanismen und zusatzlich der Wirkungsweise der einzelnen Pharmaka um so notwendiger. In diesem Kapitel sollen die Bedeutung der Tachykardie fur die Auslosung einer Myokardischamie und die Bedeutung der Herzfrequenzreduktion fur die Therapie der belastungsinduzierten Myokardischamie im Zusammenhang der zugrundeliegenden Pathophysiologie diskutiert werden.

Kurze Geschichte der Angina pectoris: Vorstellungen von der Myokardischämie im Wandel der Zeit

Die Geschichte der Angina pectoris last sich in drei wesentliche Phasen gliedern: (I) Von der Antike bis ins spate Mittelalter finden sich zahlreiche Beschreibungen einer klinischen Symptomatik, die sich in der Ruckschau als Angina pectoris beschreiben last, damals jedoch nicht mit einer Erkrankung des Herzens in Verbindung gebracht wurde. (II) In der Neuzeit wird die Angina pectoris als Erkrankung des Herzens erkannt, es werden auch erste Zusammenhange zwischen pathologischen Veranderungen der Herzkranzgefase und den klinischen Symptomen hergestellt. (III) Erst seit den 30er Jahren dieses Jahrhunderts werden im engeren Sinne pathophysiologische Konzepte der Angina pectoris entwickelt, die eine Storung der Beziehung zwischen der vom Herzen zu leistenden Arbeit und der Versorgung des Herzens durch die Kranzgefase in den Mittelpunkt stellen.

New aspects on the pathophysiology of coronary heart disease

Myocardial ischemia is the underlying pathological process for all clinical events which are referred to as coronary heart disease. Angina pectoris and myocardial infarction are the classic manifestations of myocardial ischemia. In many cases heart failure is also caused by chronic recurrent ischemia and the replacement of irreversibly injured cardiomyocytes by scar tissue (1). The initiation of malignant arrhythmias, sometimes leading to sudden cardiac death, may also be the result of myocardial ischemia.