An increase in low aortic pressure increases coronary artery flow and coronary thrombolysis induced by intravenous administration 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.

Pulmonary vascular pressure-flow characteristics. Effects of dopamine before and after pulmonary embolism.

We compared the general hemodynamic effects of dopamine and dobutamine in dogs with acute pulmonary hypertension complicated by a decrease in cardiac output (CO). The pulmonary hypertension was induced by injection of autologous blood clot. Emboli markedly increased mean pulmonary artery pressure (Ppa) and decreased CO (both p < 0.001). Both dopamine and dobutamine increased CO 50% (p < 0.05) and decreased pulmonary vascular resistance (PVR) (p < 0.05), calculated as (PAP - left ventricular end diastolic pressure)/CO. Mean PVR (mm Hg/L/min) decreased from 16.1 to 12.4 with dopamine and from 16. to 11.9 with dobutamine, both p < 0.05. Ventricular filling pressures were not affected. In another 12 dogs we investigated the effects of both drugs on pulmonary pressure-flow (P-Q) characteristics. P-Q characteristics were determined in dogs with normal Ppa values and in those with embolic pulmonary hypertension. The slope of the P-Q relationship defines the incremental vascular resistance and the extrapolated pressure intercept, the effective vascular outflow pressure. All P-Q relationships were described well by a linear equation. Despite significant systemic effects in both groups and despite a decrease in PVR with both drugs in embolized dogs, neither drug significantly affected pulmonary P-Q characteristics. The discrepancy between PVR and incremental resistance is explained by an incorrect assumption in PVR that the left ventricular filling pressure is the effective vascular outflow pressure. We conclude that both before and after the induction of pulmonary hypertension, both dopamine and dobutamine improve CO without affecting pulmonary vascular tone.

Coronary thrombolysis. Comparative effects of intracoronary administration of recombinant tissue plasminogen activator and urokinase.

We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of intracoronary administration of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) on rate and extent of coronary thrombolysis. Two doses of UK, 15,000 U/kg (UK15) and 30,000 U/kg (UK30) and two doses of rtPA, 0.25 mg/kg (rtPA.25) and 0.75 mg/kg (rtPA.75) were given. Drugs were infused over 45 min. Compared with the other regimens, rate and extent of coronary thrombolysis were significantly increased with rtPA.75. Also, despite a much higher dose of UK, coronary thrombolysis was similar with UK30 and rtPA.25. Compared with UK15, rate and extent of coronary thrombolysis were increased with rtPA.25. These results indicate that intracoronary administration of rtPA is superior to intracoronary UK in inducing thrombolysis.

Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.

We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.

Treatment of canine pulmonary hypertension: effects of norepinephrine and isoproterenol on pulmonary vascular pressure-flow characteristics.

Pulmonary vascular flow resistive properties may be described by mean pulmonary arterial pressure (PAP)-cardiac output (CO) plots. The slope of the PAP-CO relationship defines the incremental resistance and the extrapolated pressure intercept defines the effective outflow pressure. We investigated effects of norepinephrine (11 dogs) and isoproterenol (seven dogs) on the pulmonary vascular PAP-CO relationship in a model of pulmonary hypertension produced by injection of autologous blood clots. Multiple PAP-CO coordinates were obtained with and without drug infusion. CO was varied by opening systemic arteriovenous fistulas. PAP-CO relationships were well described by a linear equation (mean r value .964 +/- .032). Isoproterenol increased mean CO by 61% (p less than .01), and calculated pulmonary vascular resistance (PVR) decreased by 31% (p less than .05), corresponding to a 35% decrease (5.1 +/- 2.0 to 3.3 +/- 0.9 mm Hg X liter X min-1; p less than .01) incremental resistance. In the first seven dogs to receive norepinephrine, despite a 25% increase in blood pressure (p less than .01) no significant effects on CO, PAP, PVR, or PAP-CO relationship were observed. In the next four dogs, norepinephrine was infused at a lower dose to increase blood pressure 50% and a higher dose to ensure an increase in CO. In both conditions, calculated PVR fell (p less than .05) compared with that before norepinephrine. However, measured incremental resistance and effective outflow pressure did not change.(ABSTRACT TRUNCATED AT 250 WORDS)