Warren K. Laskey

Influence of heparin therapy on percutaneous transluminal coronary angioplasty outcome in patients with coronary arterial thrombus

The clinical and angiographic outcome of 18 patients with coronary thrombus undergoing percutaneous transluminal coronary angioplasty without antecedent heparin therapy was compared to that of a group of 35 patients receiving pre-procedural heparin therapy. The former group had a significant reduction in angiographic success (61 vs 94%, p less than 0.05) and a significant increase in immediate postprocedural thrombotic arterial occlusion (33 vs 6%, p less than 0.05). This difference existed despite equivalent frequencies of antiplatelet therapy. Prolonged intravenous heparin therapy before angioplasty in the setting of coronary thrombus improves the overall success rate and lessens the likelihood of periprocedural coronary arterial thrombosis.

Acute coronary vasoconstrictive effects of cigarette smoking in coronary heart disease

To investigate the effect of cigarette smoking on the coronary vasculature, coronary sinus flow and myocardial oxygen delivery were measured at rest and during incremental atrial pacing in 10 patients with coronary artery disease. Measurements were then repeated while the patients smoked 2 unfiltered, high-nicotine cigarettes. Although smoking significantly increased the heart rate at rest and double product, coronary sinus flow did not change significantly (141 +/- 32 vs 146 +/- 28 ml/min). At the lowest equivalent pacing rate before and during smoking, the double products were comparable. However, coronary sinus flow was reduced by smoking (146 +/- 28 vs 159 +/- 28 ml/min, p less than 0.01) and coronary vascular resistance was increased (0.96 +/- 0.15 vs 0.83 +/- 0.13 mm Hg ml-1 min, p less than 0.02). The double products were also comparable at the peak pacing rate before and during smoking. Nonetheless, the coronary sinus flow was again lower (167 +/- 23 vs 227 +/- 41 ml/min, p = 0.02) and the coronary vascular resistance was higher (0.77 +/- 0.10 vs 0.63 +/- 0.09 mm Hg ml-1 min, p less than 0.01) during smoking. The transmyocardial arteriovenous oxygen difference was unchanged by smoking; therefore, myocardial oxygen delivery was reduced in proportion to the reductions in coronary sinus flow. Thus, cigarette smoking appears to acutely alter the ability of the coronary vasculature to regulate flow in accordance with the oxygen requirements of the myocardium.

Hemodynamic changes induced by cardiac angiography with ioxaglate: Comparison with diatrizoate

The hemodynamic and electrocardiographic changes induced by left ventriculography and coronary arteriography with ioxaglate (a new low osmolality angiographic contrast agent) were characterized and compared with the changes induced by a commercial formulation of the commonly used angiographic contrast agent, diatrizoate (Renografin-76). Left ventriculography and coronary arteriography were performed in 25 patients utilizing ioxaglate and in another 25 patients utilizing diatrizoate. Both agents increased left ventricular end-diastolic pressure and decreased arteriovenous oxygen difference after left ventriculography, but the magnitude of the increase caused by ioxaglate was significantly less than that caused by diatrizoate (changes in left ventricular end-diastolic pressure was 5.3 +/- 1.3 mm Hg with ioxaglate and 9.5 +/- 1.5 mm Hg with diatrizoate [p less than 0.02] ). Change in arteriovenous oxygen difference was -0.33 +/- 0.19 ml/100 ml with ioxaglate and -0.85 +/- 0.13 ml/100 ml with diatrizoate (p less than 0.05). Both agents were well tolerated when used for coronary arteriography with no adverse events occurring in either group. Ioxaglate is a well tolerated cardiac angiographic contrast agent that produces less hemodynamic disturbance than diatrizoate. Accordingly, it may be particularly well suited to use in patients with impaired left ventricular function.

Ischemia-induced changes in human endocardial electrograms during percutaneous transluminal coronary angioplasty

The electrophysiologic sequelae of acute reversible transmural myocardial ischemia in humans are poorly understood. Experimental models have demonstrated slowing of conduction in ischemic myocardium, but similar evidence in humans is lacking. We used percutaneous transluminal coronary angioplasty as a model for reversible ischemia to (1) analyze the regional endocardial electrogram response to ischemia and (2) determine whether an initial episode of ischemia may mitigate the effects of a subsequent bout of ischemia (preconditioning). We recorded bipolar left ventricular endocardial electrograms during elective angioplasty in 11 patients and examined changes in amplitude and duration on the electrogram. Each of the 11 patients underwent two to seven balloon inflations. The electrogram amplitude at 90 seconds of balloon occlusion fell to 86% +/- 17% of the control value, and the electrogram duration increased to 109% +/- 12% of the control value. These variables returned to baseline values by 30 and 120 seconds, respectively, after balloon deflation. Among the six patients in the preconditioning protocol, the electrogram duration at 90 seconds was less with the second inflation (106% +/- 7%) than with the first (115% +/- 17%, p < 0.05). The difference in electrogram amplitude between the first and the second inflation was not significant (88% +/- 17% vs 85% +/- 13%, p = NS). At 60 seconds of ischemia there was no difference between normal sinus rhythm and paced complexes in the magnitude of change in electrogram amplitude or duration. We conclude that acute transmural myocardial ischemia in humans is associated with a decrease in local bipolar endocardial electrogram amplitude and an increase in electrogram duration. These findings are consistent with slowed conduction in the ischemic zone and are in agreement with experimental findings in animals. Furthermore, a preconditioning effect on electrogram duration suggests a possible protective effect for repeated bouts of ischemia.

Efficacy of adjunctive thrombolytic therapy in percutaneous transluminal coronary angioplasty.

Adjunctive thrombolysis has not been shown to improve angioplasty success or complication rates in elective angioplasty or myocardial infarction and may be detrimental in unstable angina. Thrombolysis of chronically occluded vessels achieves recanalization at a rate comparable to conventional angioplasty and is associated with a high rate of complications and limited long-term patency. Thrombolysis administered for thrombus or acute occlusion complicating angioplasty usually achieves coronary artery patency but is unable to forestall complications in many cases. A benefit of thrombolysis in reducing restenosis has not been conclusively demonstrated.

Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.

Effects of eliminating wave reflections on developed pressure and flow: a model based study

Absrrocr-The effects of wave reflections on the pressure and flow developed by the left ventricle were studied using an arterial svstem model coupled to a time-varying compliance simulation of the left ventricle. With this model. reflections could be reduced or eliminated while retaining the dc characteristics of the system. This allowed for the stud! of the effects of wave reflections on the dynamically beating left ventricle, without the influence of changes i n peripheral resistance. Reduction of wave reflections yields increases in peak systolic. diastolic. and mean aortic pressures and stroke volume. Stroke volume and mean pressure increased only in the range where strong reflection occurs.

Left ventricular compliance pumping and arterial system wave reflection

The effects of wave reflection alone on aortic pressure and flow were studied using an arterial system model coupled to a time-varying compliance model of the left ventricle. A reflectionless system was obtained while retaining the dc characteristics of the system. This allowed for the qualitative study of the effects of wave reflections on aortic pressure and flow. We find that in a system with reflections, diastolic pressure is decreased, allowing earlier ejection and higher peak flow. For the reflectionless case, the flow pulse is broader but stroke volume and mean aortic pressure remain the same.