Shian Gu

Intraaortic balloon counterpulsation enhances coronary thrombolysis induced by intravenous administration of a thrombolytic agent

OBJECTIVES This study was designed to test the hypothesis that in the presence of moderate hypotension, intraaortic balloon counterpulsation would enhance coronary thrombolysis induced by intravenous administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND Although many studies have confirmed the efficacy of thrombolytic therapy in acute myocardial infarction, few have systematically investigated the effects of alterations in aortic pressure on coronary thrombolysis, and none have previously investigated the effects of intraaortic balloon counterpulsation on thrombolysis. METHODS The effects of intraaortic balloon counterpulsation on aortic pressure, coronary blood flow and coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced in eight dogs by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, dogs underwent phlebotomy to decrease systolic aortic pressure to approximately 90 mm Hg. After phlebotomy, during a 15-min interval of intravenous administration of rt-PA, coronary thrombolysis and coronary flow were determined during and in the absence of counterpulsation. RESULTS Intraaortic balloon counterpulsation significantly increased aortic diastolic pressure. Corresponding to the increase in pressure, intraaortic balloon counterpulsation significantly increased the rate of rt-PA-induced coronary thrombolysis. Although not statistically significant, peak diastolic coronary flow tended to increase with counterpulsation. CONCLUSIONS These results indicate that in the presence of moderate systemic hypotension, intraaortic balloon counterpulsation enhances the rate of rt-PA-induced coronary thrombolysis.

Marked systemic hypotension depresses coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator☆

OBJECTIVES This study was designed to test the hypothesis that the level of aortic blood pressure affects the rate and extent of coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND Although many studies have confirmed the efficacy of thrombolytic therapy in the treatment of acute myocardial infarction, the effects of altered blood pressure on coronary thrombolysis have not been studied. Because the aortic pressure represents the coronary artery inflow pressure, first principles predict that changes in blood pressure will affect the delivery of the thrombolytic agent and thus affect thrombolysis. METHODS The effects of large changes in blood pressure on coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 24 dogs were classified into three groups of 8 dogs each: Group 1 dogs underwent phlebotomy to adjust systolic blood pressure to 130 mm Hg; Group 2 dogs underwent phlebotomy to decrease systolic blood pressure to 75 mm Hg. Dogs in Group 3 also underwent phlebotomy to achieve a systolic blood pressure of 75 mm Hg and then received norepinephrine to increase this pressure to 130 mm Hg. After adjustment in blood pressure, all dogs received an infusion of rt-PA (0.25 mg/kg body weight) over 30 min through the left anterior descending artery catheter. In a fourth group of six dogs, the effect of altered blood pressure on the rate of coronary thrombolysis was assessed. RESULTS In dogs in Groups 1 and 3, the rate and extent of coronary thrombolysis were significantly increased compared with values in Group 2. In each of the six Group 4 dogs the rate of coronary thrombolysis increased when norepinephrine increased systolic blood pressure from 75 to 130 mm Hg. CONCLUSIONS These results indicate that a moderate increase in coronary inflow pressure increases the rate and extent of coronary thrombolysis compared with values during marked systemic hypotension.

An Increase in Low Aortic Pressure Increases Coronary Artery Flow and Coronary Thrombolysis Induced by Intravenous Administrarion of Recombinant Tissue Plasminogen Activator

PURPOSE Our study investigated the effects of an increase in aortic pressure, induced by norepinephrine (NE) administration on coronary artery flow in a clotted artery, and rate of coronary thrombolysis induced by intravenous (i.v.) administration of recombinant tissue plasminogen activator (rtPA). METHODS A canine model of coronary thrombosis, induced by intracoronary injection of radioactive autologous blood clots, was used to test the hypothesis that an increase in aortic blood pressure will increase coronary artery flow and the rate of clot lysis induced by i.v. administration of rtPA. RESULTS After clot injection, 11 dogs were phlebotomized to decrease systolic aortic pressure to 75 mm Hg. Subsequently, .25 mg/kg of rtPA was administered intravenously over two 15-minute intervals, one during hypotension, and the other after NE infusion had increased systolic blood pressure to 130 mm Hg. In six dogs the hypotensive condition was studied first, and in five dogs the NE-induced normotensive condition was studied first. In all dogs, coronary artery flow and the rate of clot lysis were significantly increased in the normotensive condition. CONCLUSIONS These results indicate that an increase in a low coronary artery perfusion pressure may enhance coronary artery flow and the rate of thrombolysis.

Effect of Rate of Administration of Recombinant Tissue Plasminogen Activator on Efficacy of Coronary Thrombolysis

The authors employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending (LAD) coronary artery, to compare effects of different rates of administration of recombinant tissue plasminogen activator (rtPA) on efficacy of coronary thrombolysis. In one group of dogs 0.75 mg/kg of rtPA was administered via the catheter placed in the LAD coronary artery over fifteen minutes. In a second group of dogs the same dose of rtPA was admin istered over forty-five minutes. Compared with the group in which the drug was admin istered over forty-five minutes, by thirty and forty-five minutes after onset of treatment, the extent of coronary thrombolysis was significantly greater (P < 0.05) in the group who received the drug over fifteen minutes. These results demonstrate that the rate of intracoronary administration of rtPA may significantly affect thrombolytic efficacy

Effects of Progressive Vascular Occlusion on Slope and Intercept of the Pulmonary Artery Pressure-Flow Relationship

Pulmonary hemodynamics may be described by mean pulmonary arterial pressure (PAP)-cardiac output (CO) plots. The slope of the PAP-CO relationship may define the incremental resistance (IR), and the extrapolated pressure intercept (PI), the effective outflow pressure. The authors investigated the effects of progressive pulmonary vascular occlusion on the IR and PI of the PAP-CO plot. Nine experimental and nine time control dogs were studied. In the former group, PAP-CO plots were obtained in three conditions: (1) Baseline, (2) following occlusion of the right pulmonary artery, and (3) following occlusion of the right pulmonary artery and blood flow to the left upper lobe. Following progressive occlusion, there was a corresponding increase in the IR of the PAP-CO plot, from 1.95 to 3.62 to 5.16 mmHg.1-1.min (all P < 0.05). In contrast to the increase in IR, PI remained constant. Over the same interval, there were no changes in IR or PI in the time control group. These findings indicate that changes in the slope of the PAP-CO plot correspond to changes in the number of parallel vascular units.

Dobutamine enhances recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism

We used a canine model of pulmonary embolism, induced by injection of radioactive autologous blood clots, to test the hypothesis that a dobutamine-mediated increase in cardiac output (CO) would enhance recombinant tissue plasminogen activator (rtPA)-induced pulmonary thrombolysis. Emboli increased mean pulmonary artery pressure from 15 to 36 mm Hg (P < .001). There was a corresponding fall in mean CO, from 2.3 to 1.7 L/min (P < .001). Following embolization, dogs were randomly divided into three groups: group 1 dogs received rtPA, 0.5 mg/kg over 30 minutes; group 2 dogs received dobutamine prior to the same dose regimen of rtPA to increase mean CO from 1.8 to 3.4 L/min; and in group 3 dogs, prior to receiving rtPA, mean CO was increased from 1.7 to 3.2 L/min by opening a systemic arteriovenous fistula. Corresponding to the increase in CO in groups 2 and 3, the rate and extent of pulmonary thrombolysis increased. During drug infusion, the rate of pulmonary thrombolysis was 10.6% for 30 minutes in group 1 and significantly increased to 18.1 % and 21.0% for 30 minutes in groups 2 and 3, respectively. In addition, the extent of total pulmonary thrombolysis was significantly increased in groups 2 and 3 compared with group 1. While the rate of thrombolysis was similar in groups 2 and 3 during drug infusion, the extent of total thrombolysis was greater with the latter regimen. These results indicate that the combination of dobutamine and rtPA may be appropriate therapy when a low CO complicates pulmonary embolism.