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Biomedical subjects

R M Prewitt

Publications and source records attributed to R M Prewitt.

At least 19 recordsLinked to original sources
PubMed1997

Effect of a mechanical vs a pharmacologic increase in aortic pressure on coronary blood flow and thrombolysis induced by IV administration of a thrombolytic agent.

This study was designed to compare the effect of a mechanical vs a pharmacologic increase in BP on coronary artery blood flow and thrombolysis induced by IV administration of recombinant tissue plasminogen activator. We employed a canine model of coronary thrombosis induced by injection of radioactive blood clot in the left anterior descending coronary artery. Subsequently, all dogs underwent phlebotomy to decrease systolic BP to 75 mm Hg and this decreased coronary blood flow by 50%. BP was increased to 130 mm Hg by norepinephrine (NE) infusion or by inflation of a Fogarty catheter placed in the descending aorta. Interventions with NE or with a Fogarty balloon catheter increased coronary artery blood flow to similar values and rates of coronary thrombolysis were similar. However, cardiac output was significantly higher with NE. These results indicate coronary clot lysis is dependent on perfusion pressure and coronary blood flow, not cardiac output.

Animals↗
PubMed1996

Optimizing coronary thrombolysis with i.v. administration of recombinant tissue plasminogen activator. Single bolus vs double bolus vs front-loading.

This study was designed to compare the efficacy of coronary thrombolysis obtained with i.v. administration of three dose regimens of recombinant tissue plasminogen activator (rtPA). Although many studies have confirmed the efficacy of thrombolytic therapy in treatment of acute myocardial infarction, few prospective studies have been designed to determine which dose regimen optimizes the rate of coronary thrombolysis. A canine model was used. Coronary thrombosis was induced by injection of radioactive, autologous blood clots through a catheter placed in the left anterior descending coronary artery. Subsequently, 15 dogs were randomized into 3 groups of 5 dogs each. In group 1 dogs, 1.25 mg/kg of rtPA was administered i.v. as a bolus; in the group 2 dogs, 1.25 mg/kg of rtPA was administered over 60 min. The administration was "front loaded" so that 15% was administered as a bolus, 60% over 30 min, and 25% over 30 min; in group 3, 1.25 mg/kg of rtPA was divided into two i.v. boluses and administered 15 min apart. Coronary thrombolysis was assessed with a gamma camera. Despite differences in rate of administration of rtPA, at 15, 30, and 90 min after onset of treatment, extent of clot lysis was similar between groups. These results indicate that despite differences in dose regimens, rates of thrombolysis are similar when i.v. rtPA is relatively rapidly administered. Further, the similar rates of clot lysis over time between groups suggest both an effective upper limit to the dose-thrombolytic rate relationship and relatively high, sustained steady-state plasma concentrations of rtPA.

Animals↗
PubMed1995

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.

Animals↗
PubMed1995

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 (P(I)), the effective outflow pressure. The authors investigated the effects of progressive pulmonary vascular occlusion on the IR and P(I) 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, P(I) remained constant. Over the same interval, there were no changes in IR or P(I) 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.

Animals↗
PubMed1995

Intravenous administration of recombinant tissue plasminogen activator. Optimizing the rate of coronary thrombolysis.

Although many studies have confirmed the efficacy of thrombolytic therapy in treatment of acute myocardial infarction, few studies have been designed to determine which dose regimen optimizes the rate of coronary thrombolysis. This study was designed to compare the efficacy of coronary thrombolysis obtained with intravenous administration of three dose regimens of recombinant tissue plasminogen activator (rtPA). The same total dose was administered as a bolus, over 30 min, or over 90 min. A canine model was employed. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 18 dogs were randomized into 3 groups of 6 dogs each. In group 1 dogs, 0.5 mg/kg of rtPA was administered intravenously as a bolus; in the group 2 dogs, rtPA was administered intravenously over 30 min (rtPA30); in the group 3 dogs, the drug was administered over 90 min (rtPA90). Coronary thrombolysis was assessed with a gamma camera. While at 100 min, the extent of clot lysis was similar between groups, 15 and 30 min after the start of rtPA administration, coronary thrombolysis was significantly less in the rtPA90 group. These results indicate that for a given total dose of rtPA, the rate of intravenous administration may significantly affect the rate of coronary thrombolysis.

Animals↗
PubMed1995

Thrombolytic therapy in cardiogenic shock: effect of increased aortic pressure and rapid tPA administration.

OBJECTIVES: To investigate the effect of an increase in aortic pressure combined with rapid tissue plasminogen activator infusion on hemodynamic stability and patency of the infarct-related artery in patients with acute myocardial infarction complicated by profound hypotension or cardiogenic shock. BACKGROUND: Thrombolytic therapy improves mortality in relatively stable patients with acute myocardial infarction but not in patients with cardiogenic shock. Recent canine studies have demonstrated that a moderate increase in low aortic pressure improves thrombolysis. Conceivably, then, decreased thrombolytic efficacy in cardiogenic shock is due, at least in part, to a low aortic pressure impairing delivery of the thrombolytic agent. PATIENTS AND METHODS: For patients presenting within 6 h of an acute myocardial infarction complicated by profound hypotension or cardiogenic shock, an inotropic agent was rapidly administered to increase the systolic aortic pressure to approximately 110 mmHg, and 100 mg of tissue plasminogen activator was administered intravenously over 45 to 60 mins. RESULTS: Eight consecutive patients meeting the study criteria were treated over 18 months. In six of eight patients, the inotropic agent increased systolic blood pressure over 10 mins, from a mean of 64 +/- 12 mmHg to 102 +/- 12 mmHg. In the two patients whose blood pressure did not increase, early angiography in one demonstrated occlusion of the infarct-related artery, and both of the patients died. In the other six patients there was clinical and hemodynamic evidence of early reperfusion, and infarct-related arteries were patent on angiography. These six patients survived at least 30 days, with four having a favourable clinical outcome and two having a functional limitation due to heart failure. CONCLUSIONS: These results are consistent with experimental data indicating that an increase in aortic pressure combined with rapid tissue plasminogen activator infusion may increase thrombolytic efficacy when an acute myocardial infarction is complicated by profound hypotension or cardiogenic shock.

Adult↗
PubMed1994

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.

Animals↗
PubMed1994

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 administered over forty-five minutes. Compared with the group in which the drug was administered 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.

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Animals↗
PubMed1992

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.

Animals↗
PubMed1991

Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation.

We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure.

Animals↗
PubMed1991

Effects of flow on recombinant tissue plasminogen activator-induced pulmonary thrombolysis.

We employed a canine model of pulmonary embolism induced by injection of radioactive blood clots to investigate effects of changes in cardiac output (CO) on recombinant tissue plasminogen activator- (rtPA) induced pulmonary thrombolysis. Rate and extent of thrombolysis were assessed with a gamma camera. Eighteen dogs were studied. Emboli increased mean pulmonary arterial pressure and decreased CO from 2.6 to 1.9 l/min (P less than 0.001). Subsequently, dogs were randomly divided into three groups: group 1 received 0.5 mg/kg of rtPA over 30 min; 30 min before the same dose regimen of rtPA, in the six group 2 dogs, mean CO was increased to approximately 3.25 l/min by opening one systemic arteriovenous fistula; in the six group 3 dogs, before rtPA, mean CO was increased to approximately 4.5 l/min by opening two or three fistulas. After embolization, CO remained low in group 1; the mean 2-h time-averaged CO was 1.8 l/min. CO was much higher in groups 2 and 3 (3.3 and 4.6 l/min, respectively; both P less than 0.001 compared with group 1; and P less than 0.001, group 2 vs. group 3). Compared with group 1, corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in flow per se augments rtPA-induced pulmonary thrombolysis. Also, because thrombolysis was similar between groups 2 and 3, these results define an upper limit to the flow-thrombolytic relationship with rtPA.

Animals↗
PubMed1991

Coronary thrombolysis with recombinant tissue plasminogen activator. Intracoronary vs intravenous administration.

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 recombinant tissue plasminogen activator (rtPA) administered intravenously and administered directly into the coronary circulation. A control group did not receive rtPA. Compared with controls, both rtPA regimens induced coronary thrombolysis. However, compared with intravenous administration, rate and extent of coronary thrombolysis were increased with intracoronary administration. Most likely, the enhanced thrombolysis with intracoronary administration is explained by an increase in delivery of the drug to the thrombus.

Animals↗
PubMed1991

Effect of low-molecular-weight heparin on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism induced by radioactive blood clots to determine if low-molecular-weight heparin augments recombinant tissue plasminogen activator (rtPA)-induced thrombolysis. Following embolization, dogs were randomized: group 1 dogs received heparin; group 2 dogs received low-molecular-weight heparin; group 3 dogs received 1.5 mg/kg of rtPA over 45 minutes; group 4 dogs received rtPA 3 mg/kg over 45 minutes; and group 5 dogs received 1.5 mg/kg of rtPA plus low-molecular-weight heparin. Over three hours, little thrombolysis occurred in groups 1 and 2. In contrast, significant thrombolysis occurred in groups 3 to 5, 46 percent, 49 percent, and 46 percent, respectively (all p less than 0.01 compared with groups 1 and 2). We conclude that there is an upper limit to the dose-thrombolytic rate relationship with rtPA, and that low-molecular-weight heparin does not augment rtPA-induced thrombolysis.

Animals↗
PubMed1991

Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator-induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis.

Animals↗