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Compared to non-smokers, chronic smokers are at increased risk of developing atherosclerotic vascular disease, myocardial infarction, unstable angina and sudden death. The acute systemic hemodynamic response to smoking includes an increase in the heart rate, arterial pressure, cardiac output and myocardial contractility. These acute effects are primarily mediated by activation of the sympathetic nervous system. In patients with heart disease, smoking may cause a deterioration in cardiac performance. In the coronary circulation, smoking induces coronary vasoconstriction which can be prevented by alpha-adrenergic blockade, nitrates and calcium channel blockers. Non-selective beta-adrenergic blockade potentiates both the systemic and coronary vasoconstrictor effect of smoking. Other adverse effects of smoking on the cardiovascular system include a reduction in high-density lipoprotein (HDL) cholesterol, an increase in platelet reactivity and an increase in fibrinogen concentrations. These effects on systemic and coronary hemodynamics, lipid metabolism and hemostasis may contribute to the long-term adverse consequences of smoking.

The hemodynamic effects of graded-dose infusions of amrinone (maximal dose 30 micrograms/kg/min) (10 patients) and isoproterenol (maximum dose 4 micrograms/min) (11 patients) were assessed in patients with a range of left ventricular (LV) function. LV ejection fraction ranged from 0.13 to 0.77 (mean +/- standard deviation 0.47 +/- 0.23) among the patients who received amrinone and from 0.24 to 0.77 (mean 0.52 +/- 0.18) among those who received isoproterenol. Peak-dose amrinone produced a reduction in LV filling pressure (from 15 +/- 10 to 10 +/- 7 mm Hg, p less than 0.001), but no significant change in heart rate, cardiac output, mean aortic pressure, total systemic vascular resistance (TSVR) or LV dP/dt max. In contrast, peak-dose isoproterenol produced a similar reduction in LV filling pressure (from 17 +/- 12 to 13 +/- 13 mm Hg, p less than 0.05), but also caused increases in heart rate, cardiac output and LV dP/dt max and decreases in mean aortic pressure and TSVR (p less than 0.001). The absolute change in cardiac output and stroke volume correlated closely with the change in TSVR in response to amrinone (r = -0.90, p less than 0.001 and r = -0.84, p = 0.002, respectively), but not in response to isoproterenol. Although isoproterenol produced a marked increase in cardiac output and LV dP/dt max (not explained by heart rate changes alone) in all patients, amrinone produced an increase in cardiac output only in those with markedly elevated LV filling pressures (who had a reduction in TSVR), and an increase in LV dP/dt in a minority.

Because the combined use of a beta-adrenergic blocking agent and a calcium antagonist may be beneficial in some patients with severe angina, the acute hemodynamic and electrophysiologic effects of intravenous propranolol in the presence and absence of oral diltiazem treatment was studied. In 22 patients (11 men, 11 women, mean age 50 years), 12 receiving diltiazem (mean 243 mg/day, range 180 to 360) and 10 not receiving diltiazem, hemodynamic and electrophysiologic variables were measured before and 5 minutes after intravenous propranolol (0.1 mg/kg). Cardiac index (by thermodilution) and left ventricular (LV) peak dP/dt fell and LV end-diastolic pressure increased similarly in both groups. Mean systemic arterial pressure was unchanged. Coronary sinus blood flow (by thermodilution) decreased slightly in patients receiving diltiazem and was unchanged in those not receiving it. Propranolol caused a similar reduction in heart rate and increase in atrio-His conduction in both groups. Thus, when intravenous propranolol is given to patients with normal or only mildly depressed LV systolic function, the hemodynamic and electrophysiologic effects are similar in those receiving and not receiving oral diltiazem.

Previous studies suggested that cigarette smoking 1) inhibits an increase in coronary blood flow that should occur with increased myocardial oxygen demands, and 2) alters thromboxane and prostacyclin production, causing vasoconstriction and platelet aggregation. In 38 smokers (26 men and 12 women, aged 50 +/- 8 years [mean +/- standard deviation] ) with coronary artery disease, systemic and coronary hemodynamic and serologic variables were measured before and after smoking two cigarettes (in 8 to 10 minutes) (21 patients) or 8 to 10 minutes without smoking (17 patients; control group). No variable changed in the control group. Smoking increased (p less than 0.05) heart rate-systolic pressure product, cardiac output and maximal first derivative of left ventricular pressure (dP/dt) without significantly changing the coronary sinus concentrations of thromboxane B2 or 6-keto-prostaglandin F1 alpha (the stable metabolites of thromboxane A2 and prostacyclin, respectively). Smoking did not increase coronary flow in 6 of 11 patients with greater than 70% stenosis of the proximal left anterior descending or circumflex coronary artery, or both, whereas it caused an increase in coronary flow in all 10 patients without proximal stenoses (p = 0.006). To determine if smoking altered the response of coronary flow to increased myocardial oxygen demands, 10 smokers (5 men and 5 women, aged 48 +/- 9 years) underwent atrial pacing for 5 minutes followed 15 minutes later by atrial pacing for 5 minutes during smoking. In the five patients without proximal left coronary artery stenoses, coronary flow increased 26 +/- 29 ml/min with pacing and 45 +/- 21 ml/min with pacing/smoking (p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin (PGI2) is a naturally occurring vasodilator and inhibitor of platelet aggregation that produces vasodilatation of the systemic, pulmonary and coronary vascular beds in animal models. Because the endogenous production of PGI2 is reduced in those with coronary arterial disease (CAD), it may have a therapeutic role in patients with ischemic heart disease. To assess its safety and efficacy in this clinical setting, 17 patients with stable angina and CAD received an incremental intravenous infusion of either PGI2 (n = 10) to a maximum dose of 10 ng/kg/min (average 9.8 +/- 0.8 [mean +/- standard deviation]), or diluent buffer solution (placebo) (n = 7). All patients who received PGI2 became flushed, but experienced no other adverse effects PGI2 caused an increase in heart rate (66 +/- 11 to 80 +/- 11 beats/min, p less than 0.001) and cardiac index (2.88 +/- 0.65 to 3.97 +/- 1.17 liters/min/m2, p less than 0.001) and a decrease in mean femoral arterial pressure (96 +/- 18 to 86 +/- 11 mm Hg, p less than 0.001), but no change in mean pulmonary arterial or capillary wedge pressure. Total systemic and pulmonary vascular resistance decreased significantly (p less than 0.001). In response to PGI2, mean coronary sinus blood flow did not change significantly (100 +/- 40 to 121 +/- 52 ml/min), but coronary vascular resistance decreased (1.07 +/- 0.40 to 0.83 +/- 0.36 U, p less than 0.001). No variable was altered by placebo infusion. PGI2 caused a marked increase in 6-keto PGF1 alpha (the stable metabolite of PGI2) concentrations in both arterial (42 +/- 29 to 567 +/- 216 pg/ml, p less than 0.001) and venous (46 +/- 31 to 604 +/- 229 pg/ml, p less than 0.001) blood but no demonstrable change in plasma renin activity. Thus, intravenous PGI2 to a dosage of 10 ng/kg/min is a safe and effective systemic, pulmonary and coronary arterial vasodilator in patients with CAD and stable angina pectoris.

Coronary blood flow responses to nitroglycerin (NTG) in patients have been reported to be extremely variable. In dogs, NTG has a striking biphasic effect on coronary hemodynamics, consisting of a brisk increase followed by a decrease in coronary flow. To determine the effect of the drug on the coronary circulation in normal humans, NTG was injected I.C. (50 and 300 mcg) in 11 normals, and its effects on coronary flow velocity were compared to those of I. C. papaverine (6, 8, 10, and 12 mg) and saline (0.5 and 3.0 ml). Coronary flow velocity was measured using a 3F coronary Doppler catheter. The effect of each drug on coronary blood flow was analyzed in terms of both magnitude and duration (s) of the transient vasodilatory response following administration. Changes in coronary flow velocity (expressed as peak/resting velocity ratio) after 6, 8, 10, and 12 mg papaverine were (mean +/- SEM) 2.7 +/- 0.1, 3.4 +/- 0.3, 3.7 +/- 0.2, and 3.9 +/- 0.2, respectively. Very mild changes were observed with saline (1.3 +/- 0.1 and 1.7 +/- 0.1 after 0.5 and 3.0 ml, respectively), while ratios of 2.4 +/- 0.2 and 3.1 +/- 0.3 were obtained after NTG 50 and 300 mcg, respectively. The effect of 300 mcg NTG was significantly greater (p less than 0.01) than that of saline, 6 mg papaverine and 50 mcg NTG, lower than that of 12 mg papaverine and not significantly different from that of 8 and 10 mg papaverine. In terms of duration, the effect of 300 mcg NTG on coronary flow velocity was more prolonged than that of saline and 50 mcg NTG, and shorter than that of 6 to 12 mg papaverine.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was performed to assess the accuracy of qualitative angiographic grading in persons with aortic regurgitation (AR) or mitral regurgitation (MR) and to determine the factors that may influence the reliability of such grading. In 230 patients (152 men, 78 women, aged 52 +/- 14 years) with AR or MR, forward cardiac index was measured by the Fick and indicator dilution techniques and left ventricular (LV) angiographic index by the area-length method, from which the regurgitant volume index was calculated. In 124 other patients (89 men, 35 women, aged 52 +/- 11 years) without regurgitation, there was good agreement between forward and angiographic cardiac indexes (r = 0.87, p less than 0.001). In the 83 patients with AR, the regurgitant volume indexes in those with 1+ (0.87 +/- 0.57 liters/min/m2) and 2+ (1.72 +/- 1.19 liters/min/m2) angiographic regurgitation were not significantly different from one another, but were significantly different from those with 3+ (3.0 +/- 1.42 liters/min/m2) and 4+ (4.80 +/- 2.25 liters/min/m2) regurgitation; at the same time, the regurgitant volume indexes of patients with 3+ and 4+ AR were not significantly different from one another. In the 147 patients with MR, the regurgitant volume indexes in patients with 1+ regurgitation (0.61 +/- 0.64 liters/min/m2) were significantly lower than other grades, but the regurgitant volume indexes of 2+ (1.14 +/- 0.85 liters/min/m2) vs 3+ (2.14 +/- 1.37 liters/min/m2) and of 3+ vs 4+ (4.60 +/- 2.31 liters/min/m2) were not significantly different. With AR and MR, regurgitant flow within each angiographic grade varied widely, especially in grades 3+ and 4+, and there was considerable overlap of regurgitant volume indexes between grades.(ABSTRACT TRUNCATED AT 250 WORDS)