Usha Schick

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.

Acute Cardiopulmonary Effects of Nitroglycerin in Canine Oleic Acid Pulmonary Edema

In a canine model of acute respiratory failure, the authors investigated acute cardiopulmonary effects of nitroglycerin (TNG) and compared the results with those obtained after phlebotomy. Oleic acid increased intrapulmonary shunt (Qs/Qt) from 7.4 to 31% (P < 0.001) and decreased (P < 0.01) cardiac output (CO). In the presence of assumed low-pressure pulmonary edema, TNG was infused to decrease mean blood pressure (BP) by 40%; this was associated with a 26% decrease (P < 0.05) in CO. Qs/Qt increased from 31 to 42% (P < 0.01). There was a slight increase (P < 0.01) in pulmonary vascular resistance (PVR) with TNG, and mean pulmonary artery pressure (PAP) decreased (P < 0.05). In contrast, when CO was decreased by a similar amount with phlebotomy, mean Qs/Qt did not significantly change. There were similar changes in PVR and PAP and mixed venous O2 tension with TNG and phlebotomy. Accordingly, current results rule out increased flow, increased Pvo2, and mechanical alterations in pulmonary vascular pressures as contributory to the increase in Qs/Qt with TNG. Alternatively, the increase in Qs/Qt with TNG may be explained by a direct pharmacologic decrease in pulmonary hypoxic vasoconstriction and/or by nonspecific pharmacologic effects.

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.

Effects of prostaglandin E1 on the pulmonary vascular pressure-flow relationship in canine pulmonary hypertension

The effects of prostaglandin E1 (PgE1) therapy on pulmonary vascular pressure-flow relationships and gas exchange were studied in a canine model of pulmonary hypertension induced by autologous clot embolization. Dogs were subsequently ventilated with FIO2 = 1.0 (n = 6), or FIO2 = .21 (n = 6). Cardiac output (CO) was controlled by opening sytemic arteriovenous fistulas, and multiple mean pulmonary artery pressure (PAP)-CO coordinates were obtained before, during, and after PgE1. Linear regression analysis of PAP-CO plots always yielded high r values. Before PgE1, the mean slope of the PAP-CO relationship, incremental resistance, was 3.3 ± 0.9 mmHg × I−1 × min and the extrapolated pressure intercept, effective outflow pressure was 26.6 ± 5.7 mmHg. PgE1 infusion was augmented until the mean systemic arterial pressure decreased approximately 30% at both levels of FIO2. At this dose (.70 ± 34 μg/kg × min (X ± SD), PgE1 did not affect pulmonary PAP-CO characteristics or CO. In this model of canine thromboembolism, despite marked systemic effects, PgE1 did not affect pulmonary hemodynamics.

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.

Effects of altered hematocrit on pulmonary artery pressure-flow characteristics in canine pulmonary embolism☆

We used the relationship between mean pulmonary artery pressure (PAP) and cardiac output (CO) to investigate pulmonary hemodynamic effects of altered hematocrit in an intact canine model of embolic pulmonary hypertension. The slope of the PAP-CO relationship defines the incremental vascular resistance OR) and the extrapolated pressure intercept (P1) represents the effective vascular outflow pressure. Injection of autologous clot did not affect ventricular filling pressures, but decreased CO (from 3.1 to 1.9 l/min−1, P < .01) and markedly increased PAP, from 15 to 35 mm Hg (P < .01). In this setting isovolemic exchange transfusion decreased Hct from 42% to 21 % (P < .01) and markedly improved pulmonary hemodynamics. Since P1 was unaffected, this improvement was entirely explained by a decrease in the incremental vascular resistance. Hemodilution decreased IR by 25% from 4.4 to 3.3 mm Hg/l−1 /min (P < .05). We conclude that in this canine model of embolic pulmonary hypertension a decrease in viscosity significantly alters pulmonary hemodynamics by decreasing the slope of the pressure-flow relationship. These findings do not address the clinical implications of hemodilution on systemic oxygen delivery.