J.Antonio G. Lopez

Acute effect of cigarette smoking on the coronary circulation: Constriction of epicardial and resistance vessels☆

OBJECTIVES This study was performed to determine the acute effect of cigarette smoking on proximal and distal epicardial conduit and coronary resistance vessels. BACKGROUND Cigarette smoking causes constriction of epicardial arteries and a decrease in coronary blood flow in patients with coronary artery disease, despite an increase in myocardial oxygen demand. The role of changes in resistance vessel tone in the acute coronary hemodynamic effect of smoking has not been examined. METHODS Twenty-four long-term smokers were studied during cardiac catheterization after vasoactive medications had been discontinued. The effect of smoking one cigarette 10 to 15 mm long on proximal and distal conduit vessel segments was assessed before and immediately after smoking and at 5, 15 and 30 min after smoking (n = 8). To determine the effect of smoking on resistance vessels, coronary flow velocity was measured in a nonobstructed artery with a 3F intracoronary Doppler catheter before and for 5 min after smoking (n = 8). Eight patients were studied without smoking to control for spontaneous changes in conduit arterial diameter (n = 5) and resistance vessel tone (n = 3). RESULTS The average diameter of proximal coronary artery segments decreased from 2.56 +/- 0.12 mm (mean +/- SEM) before smoking to 2.41 +/- 0.09 mm 5 min after smoking (-5 +/- 2%, p < 0.05). Distal coronary diameter decreased from 1.51 +/- 0.07 to 1.39 +/- 0.06 mm (-8 +/- 2%, p < 0.01). Marked focal vasoconstriction after smoking was observed in two patients. Coronary diameter returned to baseline by 30 min after smoking. There was no change in vessel diameter in control patients. Despite a significant increase in the heart rate-mean arterial pressure product, coronary flow velocity decreased by 7 +/- 4% (p < 0.05) and coronary vascular resistance increased by 21 +/- 4% (p < 0.01) 5 min after smoking. There was no change in these variables in the control subjects. CONCLUSIONS Smoking causes immediate constriction of proximal and distal epicardial coronary arteries and an increase in coronary resistance vessel tone, despite an increase in myocardial oxygen demand. These acute coronary hemodynamic effects may contribute to the adverse cardiovascular consequences of cigarette smoking.

Comparison of coronary vasodilation with intravenous dipyridamole and adenosine

Although both intravenous dipyridamole and adenosine have been used to produce coronary vasodilation during cardiac imaging, the relative potency of the commonly administered doses of these agents has not been evaluated. Accordingly, the coronary and systemic hemodynamic effects of intravenous adenosine (140 micrograms/kg per min) and intravenous dipyridamole (0.56 mg/kg over 4 min) were compared with a maximally dilating dose of intracoronary papaverine in 15 patients. Coronary blood flow responses were assessed using a Doppler catheter in a nonstenotic coronary artery. The protocol was discontinued in two patients because of transient asymptomatic atrioventricular (AV) block during adenosine infusion. The mean heart rate increased more with adenosine (11 +/- 9 beats/min) and dipyridamole (11 +/- 7 beats/min) than with papaverine (4 +/- 3 beats/min, p less than 0.05 vs. adenosine and papaverine). The mean arterial pressure decreased less with dipyridamole (-10 +/- 3 mm Hg) and papaverine (-9 +/- 4 mm Hg) than with adenosine (-16 +/- 5 mm Hg, p less than 0.01 vs. dipyridamole and papaverine). The peak/rest coronary blood flow velocity ratio was greater with papaverine (3.9 +/- 1.1) than with adenosine (3.4 +/- 1.2, p less than or equal to 0.05 vs. papaverine) or dipyridamole (3.1 +/- 1.2, p less than 0.01 vs. papaverine). A larger decrease in coronary resistance as measured by the coronary vascular resistance index occurred with papaverine (0.25 +/- 0.06) and adenosine (0.26 +/- 0.09) than with dipyridamole (0.31 +/- 0.10, p less than 0.01 vs. papaverine, p less than 0.05 vs. adenosine).(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of leukocytes with complement C5a is associated with prostanoid-dependent constriction of large arteries in atherosclerotic monkeys in vivo

Activated leukocytes release a variety of substances which have been shown in vitro to modulate vascular tone. The chemotactic peptide complement C5a is a physiological activator of leukocytes. We injected human recombinant complement C5a (10 and 100 micrograms) into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys and examined vascular responses. In both normal and atherosclerotic monkeys, the high dose of C5a produced about 65% decrease in leukocyte cell count in venous blood drainage from the hind limb. Injection of C5a produced a pronounced increase in resistance of large arteries (segment from iliac artery to dorsal pedal artery) in atherosclerotic, but not in normal monkeys. The constrictor effect of C5a in atherosclerotic monkeys was abolished by the thromboxane A2 receptor antagonist SQ 29,548 (2 mg/kg i.v.). The platelet-activating factor antagonist WEB 2086 (5 mg/kg, i.v.) did not alter vascular responses to C5a. We conclude that activation of leukocytes produces constriction of large arteries in atherosclerotic, but not normal, monkeys in vivo. This response may be mediated in part by release of thromboxane A2.

Responses to Serotonin in Atherosclerotic and Hypertensive Blood Vessels

Vasoconstrictor responses to serotonin are potentiated in primates with diet-induced atherosclerosis and in genetically hypertensive rats. The endothelial abnormality which characterizes atherosclerotic and hypertensive arteries may contribute to the exaggerated vasoconstrictor responses to serotonin. We speculate that altered responsiveness to serotonin and other vasoactive products that are released by platelets may contribute to several clinical syndromes, including amaurosis fugax and nonocclusive mesenteric ischemia.

Constriction and Dilatation in Atherosclerotic and Hypertensive Arteries

We will emphasize three points that pertain to approaches to quantification of changes in atherosclerotic lesions.

Atherosclerosis Alters the Response to Activated Platelets and Leukocytes

This chapter addresses vasomotor consequences of atherosclerosis. The major goal of the studies is to understand the pathophysiology of spasm in atherosclerotic arteries.

Hemodynamic Consequences of Changes in the Artery Wall During Atherogenesis

The pathogenesis of coronary vasospasm has been of interest since originally proposed by Latham in 1845 (1). Prinzmetal et al. (2) described a “variant” form of angina pectoris and reintroduced the concept of coronary spasm as an important factor in some instances of rest angina. Gensini et al. (3) used coronary angiography to document for the first time appearance of spontaneous vasospasm associated with angina, in a patient with mild atherosclerotic coronary artery disease, as well as the resolution of this vasoconstriction and chest pain with administration of nitrates. Later, Guazzi et al. (4) and Maseri et al. (5) demonstrated that in “variant” angina, in contrast to typical angina, there is no increase in myocardial metabolic demand before the episodes of chest pain. Additional studies have suggested that spasm-induced decreases in myocardial perfusion are not only responsible for “variant” angina, but also lead to unstable angina, myocardial infarction and sudden death (6–7).