Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trial. Potential Class Improvement From Intramyocardial Channels.

BACKGROUND: Percutaneous transmyocardial laser revascularisation (PTMR) is a proposed catheter-based therapy for refractory angina pectoris when bypass surgery or angioplasty is not possible. We undertook a randomised trial to assess the safety and efficacy of this technique. METHODS: 221 patients with reversible ischaemia of Canadian Cardiovascular Society angina class III (61%) or IV (39%) and incomplete response to other therapies were recruited from 13 centres. Patients were randomly assigned PTMR with a holmium:YAG laser plus continued medical treatment (n=110) or continued medical treatment only (n=111). The primary endpoint was the exercise tolerance at 12 months. Analyses were by intention to treat. FINDINGS: 11 patients died and 19 withdrew; 92 PTMR-group and 99 medical-treatment-group patients completed the study. Exercise tolerance at 12 months had increased by a median of 89.0 s (IQR -15 to 183) with PTMR compared with 12.5 s (-67 to 125) with medical treatment only (p=0.008). On masked assessment, angina class was II or lower in 34.1% of PTMR patients compared with 13.0% of those medically treated. All indices of the Seattle angina questionnaire improved more with PTMR than with medical care only. By 12 months there had been eight deaths in the PTMR group and three in the medical treatment group, with similar survival in the two groups. INTERPRETATION: PTMR was associated with increased exercise tolerance time, low morbidity, lower angina scores assessed by masked reviewers, and improved quality of life. Although there is controversy about the mechanism of action, and the contribution of the placebo effect cannot be quantified, this unmasked study suggests that this palliative procedure provides some clinical benefits in the defined population of patients.

Determinants of infarct size after thrombolytic treatment in acute myocardial infarction.

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.

Cocaine-induced cardiovascular effects: lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide.

It has been suggested that cocaine acts directly in the brain to enhance central sympathetic outflow. However, some studies suggested that the cardiovascular effects of cocaine are related to a peripheral action. To characterize further the site of cocaine's cardiovascular effect, we compared the hemodynamic effects of cocaine (2 mg/kg, i.v. bolus) with those observed after administration of an equimolar dose (2.62 mg/kg, i.v. bolus) of cocaine methiodide, a quaternary derivative of cocaine that does not penetrate the blood-brain barrier, by using sufentanil-sedated dogs. Cocaine produced significant (p < 0.05) increases in heart rate (+37+/-11 beats/min), mean arterial pressure (+55+/-11 mm Hg), left ventricular end-diastolic pressure (+5.3+/-1.0 mm Hg), and cardiac output (+2.4+/-0.9 L/min). Cocaine methiodide produced increases in heart rate (+57+/-11 beats/min), mean arterial pressure (+45+/-11 mm Hg), left ventricular end-diastolic pressure (+3.4+/-1.0 mm Hg), and cardiac output (1.1+/-0.9 L/min), which were not significantly different from those observed with cocaine. Because opiate sedation potentially might have attenuated central sympathetic outflow, we further confirmed the qualitative similarity of the actions of cocaine and cocaine methiodide on heart rate and blood pressure in unsedated, conscious dogs. Our data suggest that the cardiovascular effects of cocaine result primarily from a peripheral site of action.

Value of the American College of Cardiology/American Heart Association stenosis morphology classification for coronary interventions in the late 1990s.

The goal of this study was to reassess the accuracy of the American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification for predicting coronary intervention success and complications in the era of new devices. Previous studies performed in the early part of this decade for percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease found that these criteria were predictive of success rates but not complication rates. Data for 957 consecutive coronary interventions in 1,404 lesions from June 1994 to October 1996 were prospectively classified according to ACC/AHA guidelines and entered into a database. Ninety-one and 9/10 of coronary interventions were successful, defined as <50% residual stenosis of each vessel attempted in the absence of major in-hospital complications, including Q-wave myocardial infarction, ventricular arrhythmia, need for emergency coronary artery bypass surgery, or death. Success rates did not differ between A (186 of 193, 96.3%), B1 (211 of 221, 95.5%), and B2 (676 of 711, 95.1%) lesions, but each was more successful than C (246 of 279, 88.2%) lesions (p <0.003, p < 0.004, and p = 0.0001, respectively). The class of lesion (A, B, or C) did not predict device (atherectomy, rotablator, and stent) use but specific morphologic characteristics of lesions within these classes were predictive of which device was used. Multiple regression analysis revealed that total occlusion and vessel tortuosity were predictive of procedure failure. Lesion type (A, B, or C) was not predictive of complications, but bifurcation lesions (p = 0.0045), presence of thrombus (p = 0.0001), inability to protect a major side branch (p = 0.0468), and degenerated vein graft lesions (p = 0.0283) were predictive. Thus, the ACC/AHA grading system is predictive of successful coronary intervention outcome, particularly of C-type characteristics, but not of complications or device success rate and selection. Although lesion type (A, B, or C) was not predictive of complications, specific lesion morphologies were predictive of adverse events and device use.

Does low individual operator coronary interventional procedural volume correlate with worse institutional procedural outcome?

OBJECTIVES: To assess the relation between individual operator coronary interventional volume and incidence of complications, the in-hospital outcome at a single, moderate volume urban academic center was prospectively collected over a 3-year period. BACKGROUND: A minimum of 75 coronary interventions/operator per year may be required in the future to obtain formal certification. However, few data exist regarding individual operator volumes and procedural outcome. METHODS: Between January 1993 and December 1995, 1,389 consecutive procedures were performed or supervised by nine geographic full-time operators: 171 (12.3%) utilized various devices, and 350 (25.2%) involved multivessel coronary intervention. Left ventricular ejection fraction was 59 +/- 15% (mean +/- SD), and there were 1.7 +/- 0.7 vessels diseased (with > or = 70% stenosis). Clinical indications included stable angina in 22.5% of cases, unstable angina in 31.9%, acute myocardial infarction (MI) in 2.9%, post MI in 20.6%, shock or acute heart failure in 3.0% and restenosis in 19.1%. In the last consecutive 857 lesions in 655 cases, 20.7% type A, 55.5% type B and 23.8% type C lesions were categorized before coronary intervention. RESULTS: Average yearly operator volume ranged from 26 to 83 cases (mean 51 +/- 26). Each operator has performed a total of 590 +/- 268 coronary interventions, with 10.0 +/- 4.3 years of coronary interventional experience. The mean angioplasty volume rating for the nine operators was 180 +/- 37 (> 170 considered adequate). The in-hospital major complication rate was 1.4% (95% confidence interval 0.7% to 1.893%) for all coronary interventions, including death in 3 patients, bypass surgery in 13, arrhythmia in 3 and Q wave MI in 2. To ascertain how these outcomes compared with standard measures of coronary interventional outcome, four previously published registries were reanalyzed in a similar manner. The rate of complications in the present study was found to be significantly lower than that of the 1992-1993 Society for Cardiac Angiography and Intervention registry (1.9%, n = 19,594, p < 0.05 [excludes ventricular arrhythmias]), the 1994 American College of Cardiology database (3.9%, n = 38,963, p = 0.001), the Mid-America Heart Institute outcome in 1988 (2.3%, n = 5,413, p = 0.02) and the 1985-1986 National Heart, Lung, and Blood Institute Registry (7.2%, n = 1,801, p = 0.001). Odds ratios and 95% confidence intervals showed the outcome in the current study to be at least comparable to the standard registries. CONCLUSIONS: Despite individual operator volumes below those currently being considered for credentialing, the overall institutional outcome was excellent in a diverse and complex patient population.

Cardiac endothelin release and infarct size, myocardial blood flow, and ventricular function in canine infarction and reperfusion.

BACKGROUND: The potent vasoconstrictor endothelin-1 (ET) may play an important pathophysiologic role in acute myocardial infarction, but its precise effects are incompletely understood. The purpose of this study was to evaluate the interrelationships between cardiac ET-1 release and infarct size, myocardial blood flow, and ventricular function. METHODS: Fifteen closed chest dogs underwent 3 hours of coronary artery occlusion followed by 3 hours of reperfusion. Coronary sinus and aortic ET-1 levels during occlusion and after reperfusion were determined by radioimmunoassay. Left ventricular function and regional myocardial blood flow were measured by echocardiography and colored microspheres, respectively. Myocardial infarct size was determined by postmortem staining with blue dye and triphenyl tetrazolium chloride. RESULTS: Coronary occlusion and reperfusion produced significant elevations of coronary sinus ET-1 (p < 0.05) and cardiac ET-1 release (p < 0.05), and a trend toward an increase in aortic ET-1 (p = 0.08). A trend toward more ET-1 release was observed in dogs with larger infarcts (p = 0.06), and in dogs with substantial no-reflow in the reperfused territory (p = 0.05). Endothelin-1 release also was associated with increased contractility in nonischemic myocardial segments (p = 0.002), and ET-1 correlated with increased global left ventricular function (p < 0.02). CONCLUSIONS: In this canine model of coronary occlusion and reperfusion, greater increases in cardiac ET-1 release were observed in dogs with larger infarcts, and increased ET-1 release was associated with the no-reflow phenomenon in the reperfused territory. These data suggest that ET-1 release may have adverse consequences in acute myocardial infarction, including a reduction of myocardial blood flow in the reperfused zone after reperfusion and increased contractility in nonischemic myocardium.

Poloxamer-188 as an adjunct to primary percutaneous transluminal coronary angioplasty for acute myocardial infarction.

Poloxamer-188 is a surfactant polymer with antithrombotic and hemorheologic properties that make it potentially useful as an adjunct to acute reperfusion strategies. Animal studies and early human studies have documented poloxamer-188 to be effective at improving myocardial salvage when used as an adjunct to intravenous thrombolytic therapy for acute myocardial infarction. The current trial was a prospective pilot study involving 150 patients who were randomized in a 2:1 fashion to a poloxamer-188 infusion for 48-hours versus placebo. The poloxamer-188 infusion was well tolerated subjectively. The only clinically significant laboratory abnormality noted was an elevation in the serum creatinine above 2.0 g/dl in 12% (n = 12) of the 98 poloxamer-188 treated patients versus 1 of the 52 (2%) of the placebo treated patients (p = 0.048). Clinical end points including reinfarction (1% vs 4%), cardiogenic shock (7% vs 6%), and death (9% vs 4%) were statistically similar in the poloxamer-188 and placebo groups, respectively (p = NS). Using quantitative nuclear techniques, final infarct size and myocardial salvage were statistically similar in the poloxamer-188 and placebo groups. Mean left ventricular ejection fractions 1 week post after infarction were 51% +/- 12% in the poloxamer-188 group and 52% +/- 13% in the placebo group (p = NS). Final infarct size, was not altered by the poloxamer- 188 infusion; however, it was significantly correlated with normal perfusion (Thrombolysis in Myocardial Infarction grade 3 flow) in the infarct vessel after angioplasty. This study documented poloxamer-188 to be ineffective as an adjunct to primary angioplasty for acute myocardial infarction and resulted in azotemia in 12% of the patients.

Beneficial effects of RheothRx injection in patients receiving thrombolytic therapy for acute myocardial infarction. Results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: RheothRx (poloxamer 188) is a surfactant with hemorheological and antithrombotic properties that reduces myocardial reperfusion injury in animal models of myocardial infarction. The purpose of the present study was to evaluate the safety and efficacy of adjunctive therapy with poloxamer 188 in patients receiving thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: In this multicenter trial, we randomized 114 patients to a 48-hour infusion of poloxamer 188 or vehicle placebo beginning immediately after the initiation of thrombolytic therapy. Tomographic imaging with 99mTc sestamibi before reperfusion and again 5 to 7 days after the infarction was used to determine myocardium at risk for infarction, infarct size, and myocardial salvage. Radionuclide angiography at 5 to 7 days after infarction was used to measure left ventricular ejection fraction. The treated and control groups had comparable baseline characteristics, time to thrombolytic administration, and time to treatment with poloxamer 188 or placebo. Poloxamer 188-treated patients demonstrated a 38% reduction in median myocardial infarct size (25th and 75th percentile) compared with placebo (16% [7, 30] versus 26% [9, 43]; P = .031), greater median myocardial salvage (13% [7, 20] versus 4% [1, 15]; P = .033), and a 13% relative improvement in median ejection fraction (52% [43, 60] versus 46% [35, 60]; P = .020). Poloxamer 188 treatment also resulted in a reduced incidence of reinfarction (1% versus 13%; P = .016). Poloxamer 188 was well tolerated without adverse hemodynamic effects or significant organ toxicity. CONCLUSIONS: Adjunctive therapy with poloxamer 188 resulted in substantial benefit in this randomized trial, including significantly smaller infarcts, greater myocardial salvage, better left ventricular function, and a lower incidence of in-hospital reinfarction. Although the mechanisms are unproven, poloxamer 188 treatment may accelerate thrombolysis, reduce reocclusion, and ameliorate reperfusion injury.

Effect of 100% oxygen administration on infarct size and left ventricular function in a canine model of myocardial infarction and reperfusion.

High oxygen concentrations reduced infarct size in prereperfusion era studies; however, with reperfusion therapy, high oxygen tension carries the theoretical risk of exacerbating reperfusion injury by increasing toxic oxygen-derived free radicals. In this study, two groups of dogs underwent 90 minutes of coronary occlusion and 72 hours of reperfusion. The oxygen group (n = 16) received 100% inspired oxygen from 20 minutes before reperfusion through 3 hours of reperfusion, whereas the room-air group (n = 19) was ventilated with room air. Infarct size (as a percentage of risk area) was reduced by 38% in the oxygen group (26.7% +/- 4.7% vs 43.3% +/- 4.3%; p = 0.017). This benefit was independent of underlying variability in collateral blood flow in individual dogs (p = 0.016 by analysis of covariance [ANCOVA]). Left ventricular ejection fraction was significantly improved in the oxygen group (43% +/- 3% vs 33% +/- 2%; p = 0.008), as was regional function in the infarct zone (p < 0.05). These data suggest that high concentrations of inspired oxygen may also benefit patients with acute myocardial infarction who undergo reperfusion therapy.

Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function.

BACKGROUND: Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration. METHODS AND RESULTS: Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 +/- 4.2% versus 43.3 +/- 4.3%, P D .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 +/- 4.3%, P = .08). ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P = .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P < .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 +/- 3.1% versus 33 +/- 2.0%, P < .05), whereas ejection fraction in the 4-hour group was 37 +/- 1.3% (P = NS versus control). Regional ventricular function was also significantly better in the 48-hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action. CONCLUSIONS: A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours.

Additive myocardial depressant effects of cocaine and ethanol.

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.

Excimer laser ablation before autoperfusion balloon inflation: a novel therapeutic approach to high grade stenoses in vessels supplying substantial myocardium at risk.

The utility of a novel approach employing excimer laser ablation to form a channel for subsequent autoperfusion balloon angioplasty is presented. Two important advantages of this strategy are highlighted: (1) applicability to severe stenoses in vessels supplying substantial myocardium at risk and (2) ability to allow prolonged inflation time to minimize procedure related ischemia and optimize revascularization of the heart. We prospectively selected and studied five patients and performed excimer laser coronary angioplasty using either a 1.3 mm or 1.6 mm laser catheter followed by autoperfusion balloon dilatation. Procedural success was documented by a significant reduction in mean percent diameter stenosis from 89 +/- 4% (S.D.) to 53 +/- 4% after laser angioplasty (p < 0.0001) and subsequently to 20 +/- 4% after autoperfusion balloon angioplasty (p < 0.0001). Clinical success was attained and characterized by resolution of anginal symptoms for at least 4 weeks after hospital discharge. There were no major acute complications encountered; however, restenosis has occurred in 2 out of 5 patients. We therefore recommend this novel pre-dilation strategy with excimer laser followed by autoperfusion balloon angioplasty in selected patients with an extensive amount of myocardium at risk.

Cocaine produces coronary artery vasoconstriction independent of an intact endothelium.

Studies have demonstrated that cocaine causes coronary vasoconstriction, but this has been unassociated with myocardial ischemia. Therefore, cocaine seems unlikely to precipitate myocardial infarction in the absence of potentiating factors. We hypothesized that injury to coronary endothelium could potentiate cocaine-induced coronary vasoconstriction by decreasing EDRF. The effect of cocaine on LAD diameter was measured in dogs subjected to coronary endothelial denudation and compared with that in a non-denuded control group. Endothelial denudation was accomplished by abrasion with an inflated angioplasty balloon and confirmed in vivo by demonstrating a vasoconstrictive response to infused acetylcholine and by postmortem scanning electron microscopy. Cocaine produced a similar maximal reduction in LAD diameter in both groups. Thus, cocaine induces endothelium-independent coronary artery vasoconstriction. Failure of endothelial injury to potentiate the coronary vasoconstrictive effect by cocaine suggests that factors other than endothelial dysfunction may be important in pathogenesis of cocaine-associated myocardial infarction.

Effect of cocaine on the coronary circulation and systemic hemodynamics in dogs.

This study investigated the effect of intravenous cocaine (0.5 to 2 mg/kg body weight) on the coronary circulation and systemic hemodynamics in closed chest sedated dogs. The role of alpha- and beta-adrenoceptor stimulation in mediating these effects was also investigated. Cocaine produced dose-dependent increases in mean arterial pressure and rate-pressure product. Although the lower doses of cocaine had no significant effect on the coronary circulation, the 2 mg/kg dose produced a 55 +/- 14% increase in coronary vascular resistance (p less than 0.05 versus baseline) and a 19 +/- 3% reduction in diameter of the left anterior descending coronary artery (p less than 0.05 versus baseline). Despite these potentially deleterious effects on the coronary circulation (occurring at a time of markedly increased myocardial oxygen demand), the electrocardiogram did not demonstrate ischemic changes and there was no myocardial lactate production. Cocaine-induced coronary vasoconstriction was abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, but not by pretreatment with the beta-adrenoceptor antagonist propranolol. The findings that cocaine did not change systemic vascular resistance in dogs without adrenergic blockade, reduced systemic vascular resistance in dogs after alpha-blockade (p less than 0.05) and increased systemic vascular resistance in dogs after beta-blockade (p = 0.06) suggest that epinephrine (rather than norepinephrine) is primarily responsible for the peripheral vascular actions of cocaine. Thus, in this canine preparation with normal coronary arteries, cocaine produced vasoconstriction of both epicardial and coronary resistance vessels that was not associated with evidence of myocardial ischemia. The pharmacologic mechanism for the effect of cocaine on the coronary circulation is alpha-adrenoceptor stimulation, whereas systemic hemodynamic effects are mediated by combined alpha- and beta-adrenoceptor stimulation.

Detection of renal blood flow abnormalities in septic and critically ill patients using a newly designed indwelling thermodilution renal vein catheter.

To evaluate alterations in renal blood flow in sepsis-induced renal failure, we developed and studied a percutaneously placed thermodilution renal blood flow catheter in eight critically ill patients. Para-aminohippurate extraction coefficients were decreased, supporting the need for renal vein sampling to determine CPAH in sepsis. Thermodilution and CPAH methods correlated strongly, confirming the reliability of this thermodilution method. Renal vascular resistance, an indicator of renal vascular function, remained unchanged throughout the bouts of sepsis. The fraction of total body arterial blood flow going to the kidneys rose significantly during recovery from sepsis. Glomerular filtration rate, which was reduced in four of seven septic patients, correlated with the fraction of total blood flow going to the kidneys. These results suggest that renal vascular abnormalities may be occurring during septic shock. Our study demonstrates that sepsis-induced renal dysfunction may occur despite normal ranges of total renal blood flow during shock.