In: Aortic Pressure11 Jan 2014
Our study compared left anterior descending coronary artery flows and rates of coronary thrombolysis when systolic BP was pharmacologically increased with norepinephrine infusion or mechanically increased by inflation of a Fogarty catheter in the descending aorta. Systolic BP increased to a similar value with both interventions. Corresponding to the similar systolic BPs, diastolic BPs increased and thus led to an increased and similar left anterior descending blood flow. At similar rates of coronary blood flow, rates of coronary thrombolysis were similar. A recent study investigated the effects of phlebotomy-induced hypotension, and normotension subsequently achieved with norepinephrine infusion, on coronary thrombolysis induced by intracoronary administration of rtPA.
Compared with the hypotensive condition, coronary thrombolysis increased when norepinephrine increased systolic BP to normal values. We postulated that the increase in coronary thrombolysis was most likely due to increased delivery of the thrombolytic agent to the thrombus due to increased left anterior descending artery flow. A subsequent canine study confirmed this hypothesis. Similarly, another recent study demonstrated that in the presence of moderate hypotension (systolic BP of 90 mm Hg), intra-aortic balloon counterpulsation increased aortic diastolic pressure and the rate of coronary thrombolysis induced by IV administration of rtPA. generic clarinex
Current and recent studies are predicted by physiologic parameters governing flow in totally and subtotally obstructed vessels. That is, since the aortic pressure is the coronary inflow pressure, in subtotally occluded vessels (Thrombolysis in Myocardial Infarction Trial, Phase I), coronary flow is proportional, at least over a given range, to the driving pressure and inversely proportional to the regional vascular resistance. Therefore, changes in aortic pressure should affect delivery of the thrombolytic agent and thus thrombolysis. Further, an increase in aortic and thus transmural coronary artery pressure could convert a totally obstructed artery into one with subtotal obstruction, a condition that would decrease regional vascular resistance and enhance thrombolysis.
Even though there is not an obligatory increase in coronary artery flow when CO increases, we and others have considered the potential role of CO itself in influencing coronary thrombolysis. In the current study, while systolic BPs, left anterior descending artery blood flows, and thrombolysis were similar with norepinephrine and Fogarty catheter inflation, CO was much higher with norepinephrine.
Therefore, current results indicate that, independent from CO, it is the aortic pressure that influences coronary thrombolysis.
The current results demonstrate that systolic BPs, left anterior descending artery blood flows, and rates of thrombolysis were similar with norepinephrine and Fogarty catheter inflation. Aortic diastolic pressure was slightly lower during norepinephrine infusion than balloon inflation. It may be argued that norepinephrine may have been associated with slight coronary artery vasodilatation in view of the lower aortic diastolic pressure and similar left anterior descending artery blood flow. Nevertheless, at similar anterior descending artery blood flow, clot lysis was not significantly different (Fig 4).
Although thrombolytic therapy decreases mortality in most patients with acute myocardial infarction, this approach does not decrease mortality in patients with cardiogenic shock. The failure of thrombolytic therapy to decrease mortality in this subset of patients may be due to a low BP impairing the delivery of the thrombolytic agent to the thrombus. One retrospective clinical report described a decrease in thrombolytic efficacy with intracoronary streptokinase in patients with cardiogenic shock. As cited above, similar results are reported in recent canine studies characterized by systemic hypotension. In addition to decreased thrombolytic efficacy, it is possible that the discouraging survival rate for patients with cardiogenic shock treated with thrombolytic therapy may also be partially explained by high reocclusion rates.
While as cited above, we favor increased delivery of the thrombolytic agent mediated by an increase in aortic pressure as the explanation for our results, it is possible that the increase in left anterior descending artery blood flow washed out or diluted clotting factors in the vicinity of the thrombus, thus minimizing the incorporation of fibrin into the thrombus. Finally, it is conceivable that a pressure-mediated increase in coronary blood flow may have caused fragmentation and washout of thrombus. Although we consider these latter two possibilities unlikely, our data do not allow us to rule them out.
There are obvious differences between the model of coronaiy thrombosis employed in the current study and acute myocardial infarction that occurs clinically. For example, in the current study, coronaiy thrombosis was induced by employing exogenously produced clot delivered through an indwelling catheter. Also, there is no underlying vascular abnormality at the site of thrombus in our model. In addition, the systemic hypotension complicating acute myocardial infarction is not due to phlebotomy. Because of these factors, we recommend caution in human clinical investigations in application of our results.
Despite the shortcomings cited, we stress that the current study is the first (to our knowledge) to systematically investigate the effects of mechanical vs pharmacologic changes in BP on coronary blood flow and coronary thrombolysis. Current and recent results highlight the importance of ensuring an adequate BP when thrombolytic therapy is administered.
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