Gordon L. Pierpont

Heart rate recovery post-exercise as an index of parasympathetic activity.

The time constant (T) obtained by fitting post-exercise heart rate (HR) recovery to a first order exponential decay curve has been promoted as an index of parasympathetic activity. However, acceptance has been limited because reported data are inadequate to assess goodness of fit for the model, determine the best exercise protocol, or optimize the duration of post exercise monitoring. Consequently, we evaluated T for nine healthy volunteers (age 24-46) following treadmill exercise at maximal (max) and two stages sub-max exercise (Bruce protocol). T stabilized only after 3 min of post-exercise monitoring. With max exercise, T varied unacceptably with small changes in onset of monitoring, e.g. -16.7+/-16.6 (-13.2%) in the first 5 s, and residuals of the fitted curve were non-random. In contrast, sub-max exercise produced consistent T values, e.g. -1.9+/-3.2 (-4.2%) in the first 5 s, and residuals were more nearly random. In conclusion, first order decay is an inadequate model for HR recovery following max exercise, but may be reasonable for sub-max levels.

Hemodynamic Improvement after Oral Hydralazine in Left Ventricular Failure: A Comparison with Nitroprusside Infusion in 16 Patients

Hydralazine was administered in a single oral dose of 50 to 100 mg in 16 patients with left ventricular failure due to cardiomyopathy. It produced sustained effects for at least 4 h characterized by a significant increase in cardiac output, a reduction in arterial and pulmonary arterial pressure, and a slight rise in heart rate. When compared to nitroprusside infusion in these same patients, hydralazine produced a similar reduction in systemic vascular resistance but a slightly greater increase in cardiac index (0.74 versus 0.95 litres/min-m2), with a lesser fall in mean arterial pressure (7.8 versus 13.6 mm Hg, P less than 0.01), mean pulmonary arterial pressure (4.2 versus 11.3 mm Hg, P less than 0.001), and pulmonary wedge pressure (5.5 versus 9.9 mm Hg, P less than 0.001). Forearm venous tone decreased and venous compliance increased during nitroprusside infusion, but they were unchanged after hydralazine therapy. These data suggest that hydralazine may be a useful agent in the treatment of chronic left ventricular failure.

Predictors and outcomes of a perioperative myocardial infarction following elective vascular surgery in patients with documented coronary artery disease: results of the CARP trial.

AIMS The predictors and outcomes of patients with a peri-operative elevation in cardiac troponin I above the 99th percentile of normal following an elective vascular operation have not been studied in a homogeneous cohort with documented coronary artery disease. METHODS AND RESULTS The Coronary Artery Revascularization Prophylaxis (CARP) trial was a randomized trial that tested the benefit of coronary artery revascularization prior to vascular surgery. Among 377 randomized patients, core lab samples for peak cardiac troponin I concentrations were monitored following the vascular operation and the blinded results were correlated with outcomes. A peri-operative myocardial infarction (MI), defined by an increase in cardiac troponin I greater than the 99th percentile reference (> or =0.1 microg/L), occurred in 100 patients (26.5%) and the incidence was not dissimilar in patients with and without pre-operative coronary revascularization (24.2 vs. 28.6%; P = 0.32). By logistic regression analysis, predictors of MI (odds risk; 95%CI; P-value) were age >70 (1.84; 1.14-2.98; P = 0.01), abdominal aortic surgery (1.82; 1.09-3.03; P = 0.02), diabetes (1.86; 1.11-3.11; P = 0.02), angina (1.67; 1.03-2.64; P = 0.04), and baseline STT abnormalities (1.62; 1.00-2.6; P = 0.05). At 2.5 years post-surgery, the probability of survival in patients with and without the MI was 0.73 and 0.84, respectively (P = 0.03, log-rank test). Using a Cox proportional hazards regression analysis, a peri-operative MI in diabetic patients was a strong predictor of long-term mortality (hazards ratio: 2.43; 95% CI: 1.31-4.48; P < 0.01). CONCLUSION Among patients with coronary artery disease who undergo vascular surgery, a peri-operative elevation in cardiac troponin levels is common and in combination with diabetes, is a strong predictor of long-term mortality. These data support the utility of cardiac troponins as a means of stratifying high-risk patients following vascular operations.

d-lactate encephalopathy

Although D-lactate is not a product of human intermediary metabolism, absorption of D-lactate produced by abnormal intestinal bacteria can cause systemic acidosis in patients who have undergone gastrointestinal surgery, particularly jejunoileal bypass. In order to learn more about the prevalence of D-lactate encephalopathy, its occurrence in other disorders, and how well D-lactate concentration correlates with clinical symptoms, serum D-lactate levels were determined in several specific populations. D-lactate was undetectable (less than 0.5 mmol/liter) in 72 healthy volunteers and 57 obese persons. In 33 patients who had jejunoileal bypass, 16 reported symptoms consistent with D-lactate encephalopathy since surgery. Nine of these 16 had D-lactate levels greater than 0.5 mmol/liter (range 0.7 to 11.5 mmol/liter). Levels of D-lactate fluctuated over time, and in two patients, markedly elevated levels correlated with an encephalopathy accompanied by hyperchloremic metabolic acidosis and elevated anion gap. In 470 randomly chosen hospitalized patients, D-lactate level greater than 0.5 mmol/liter was found in 13 (2.8 percent), and 60 percent of these had a history of gastrointestinal surgery or disease. It is concluded that elevated serum D-lactate levels are relatively common in patients with jejunoileal bypass, and although more rare, occur in other gastrointestinal disorders as well. The symptoms of D-lactate encephalopathy are quite sensitive, but not necessarily specific for this disorder.

Effect of captopril on renal function in patients with congestive heart failure.

Angiotensin converting enzyme inhibitors can improve haemodynamics in patients with congestive heart failure and may enhance sodium excretion in hypertensive patients. In a metabolic unit we assessed the effects of one of these agents on renal function in nine patients with stable New York Heart Association functional class 3 or 4 congestive heart failure. Single blinded, the patients received placebo for three days, 25 to 100 mg of captopril three times a day for three days, and three more days of placebo. Mean blood pressure decreased during captopril, with little change in heart rate or respiration. Serum urea was slightly higher during captopril administration. The mean change in creatinine clearance during captopril was insignificant, but it decreased more than 25% in three of nine patients. Decreases in creatinine clearance correlated with lower blood pressure during captopril and were most obvious in patients with high baseline plasma renin activity. Urine output and both sodium and potassium excretion decreased during captopril. Thus captopril failed to improve natriuresis in patients with congestive heart failure and close monitoring of kidney function is necessary when using this agent in patients with congestive heart failure, particularly when blood pressure falls to lower levels.

Usefulness of Revascularization of Patients With Multivessel Coronary Artery Disease Before Elective Vascular Surgery for Abdominal Aortic and Peripheral Occlusive Disease

The Coronary Artery Revascularization Prophylaxis (CARP) study showed no survival benefit with preoperative coronary artery revascularization before elective vascular surgery. The generalizability of the trial results to all patients with multivessel coronary artery disease (CAD) has been questioned. The objective of this study was to determine the impact of prophylactic coronary revascularization on long-term survival in patients with multivessel CAD. Over a 4-year period, 1,048 patients underwent coronary angiography before vascular surgery during screening into the CARP trial. The cohort was composed of registry (n = 586) and randomized (n = 462) patients, and their survival was determined at 2.5 years after vascular surgery. High-risk coronary anatomy without previous bypass surgery included 2-vessel disease (n = 204 [19.5%]), 3-vessel disease (n = 130 [12.4%]), and left main coronary artery stenosis > or = 50% (n = 48 [4.6%]). By log-rank test, preoperative revascularization was associated with improved survival in patients with a left main coronary artery stenoses (0.84 vs 0.52, p <0.01) but not those with either 2-vessel (0.80 vs 0.79, p = 0.83) or 3-vessel (0.79 vs 0.71, p = 0.15) disease. In conclusion, unprotected left main coronary artery disease was present in 4.6% of patients who underwent coronary angiography before vascular surgery, and this was the only subset of patients showing a benefit with preoperative coronary artery revascularization.

Effects of vasodilators on pulmonary hemodynamics and gas exchange in left ventricular failure

Abstract Nitroprusside (NP) has been shown to improve left ventricular function in patients with congestive heart failure, but despite an increased cardiac output and decreased pulmonary capillary pressure, arterial oxygen tension (P a O 2 ) may fall. In order to determine the mechanism of this hypoxemia, and to determine if similar effects occur with non-parenteral vasodilators, hemodynamic, respiratory, and blood gas responses to NP, hydralazine (H), and hydralazine combined with isiosorbide dinitrate (H+N) were studied in 10 patients with left ventricular failure. At the dosages used, all three drug regimens increased cardiac output equivalently, but pulmonary vascular responses differed. NP and H+N decreased mean pulmonary artery pressure, pulmonary wedge pressure, and pulmonary arteriolar resistance, while H did not. NP decreased P a O 2 by 10.4 mm. Hg (p a O 2 . Arteriolar-alveolar oxygen gradient increased with NP (150 ± 39 per cent, p a O 2 . Changes in arteriolar-alveolar oxygen gradient correlate with the changes in pulmonary arteriolar resistance. Thus vasodilators which have prominent pulmonary vascular effects can decrease P a O 2 in patients with congestive heart failure, and this effect is most likely due to increasing ventilation-perfusion inequities.

Electrophysiologic characteristics of a pulsed iontophoretic drug-delivery system in coronary arteries

This study evaluated the electrophysiologic effects of a pulsed iontophoretic drug-delivery system when used in the coronary arteries. Prevention of acute thrombosis and restenosis after intravascular procedures may be enhanced by high concentrations of therapeutic agents within the vessel wall. A new intravascular drug-delivery system uses iontophoresis to maximize local tissue concentrations of drug. However, the electrophysiologic effects of such a system in coronary arteries are unknown. An iontophoretic membrane balloon-tipped catheter was placed fluoroscopically in the mid left anterior descending coronary artery of 10 anesthetized dogs. Strength-duration curves and effective refractory period (ERP) were initially determined. Threshold for capture was assessed at pulse widths of 0.5, 1.0, 2.0, 4.0, and 8.0 ms. Capture occurred at 4.9 +/- 0.9, 3.4 +/- 0.5, 2.6 +/- 0.5, 1.6 +/- 0.2, and 1.2 +/- 0.2 mA, respectively. The ERP was 169 +/- 6 ms (4.0-ms pulses at twice threshold). Then square-wave pulses for iontophoresis were R-wave synchronized and delivered at 50 and 75% of the ERP with the balloon inflated to 1 atm. Output was increased until significant arrhythmias occurred [premature beats > 10/min, supraventricular tachycardia (SVT), ventricular tachycardia (VT), ventricular fibrillation (VF)], by using sequential steps of 1, 5, 10, 15, and 20 mA. Highest average outputs achieved without an arrhythmia were 14.1 +/- 2.5 and 4.9 +/- 2.0 mA at 50 and 75% of ERP, respectively (p < 0.05). High-grade arrhythmias (pulseless VT or VF) occurred in three of four animals studied before use of a frequency limiter, which allowed current delivery only at intervals > 400 ms (thus inhibiting current activation during premature beats). No further VT or VF occurred in the remaining six animals, except for one episode of nonsustained VT (11 beats). An R-wave synchronized iontophoretic field with a response-frequency limiter can be safely used within the canine coronary arterial system at 50% of ERP with moderate outputs (5-10 mA). Increasing the stimulus duration to 75% of ERP increases arrhythmogenesis but is tolerated at lower output levels (< 5 mA).

“Maximal” drug therapy is not necessarily optimal in chronic angina pectoris

Beta-adrenergic blocking agents, nitrates and calcium channel antagonists are effective in treating angina pectoris, but much remains unknown about how they act in combination. Consequently, treadmill exercise was used to assess the relative efficacy of nifedipine or isosorbide dinitrate, or both, in 19 patients with stable angina receiving propranolol. Propranolol therapy was continued and either placebo, nifedipine (20 mg), isosorbide dinitrate (20 mg) or both drugs were given randomly 1 1/2 hours before exercise in a double-blind trial. In 16 patients who completed the protocol, heart rate at rest during propranolol therapy was 53.7 +/- 1.9 beats/min (mean +/- standard error of the mean); it increased 4.6 +/- 1.2 beats/min with the addition of nifedipine (p less than 0.01), but was unchanged with isosorbide dinitrate or both combined. Compared with values during treatment with propranolol alone, systolic blood pressure at rest decreased with each vasodilator individually and when combined. Rate-pressure product at maximal exercise was the same with all combinations. Exercise duration was 467 +/- 50 seconds with propranolol, increased to 556 +/- 47 seconds with isosorbide dinitrate (p less than 0.05) and to 636 +/- 50 seconds with nifedipine (p less than 0.001). Exercise duration with all three drugs was 597 +/- 47 seconds (p less than 0.01 compared with propranolol alone). The improvement with nifedipine was greater than with isosorbide dinitrate (p less than 0.05) but exercise duration was not significantly different with the combination of these drugs than when either drug was used alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneous myocardial catecholamine concentrations in patients with congestive heart failure.

Left ventricular catecholamine and plasma norepinephrine levels were assayed in 39 patients undergoing cardiac transplantation to test the hypothesis that in congestive heart failure (CHF) the normally high concentration of myocardial norepinephrine is depleted while dopamine is increased because dopamine conversion to norepinephrine is the rate-limiting step in norepinephrine synthesis. Plasma norepinephrine was elevated in all patients (average 741 +/- 472 micrograms/ml), but myocardial norepinephrine was variable, ranging from 79 to 2,127 ng/g (average 512 +/- 392). Myocardial dopamine also varied considerably (range 0 to 713 ng/g, average 143 +/- 150). Nineteen patients had the expected pattern of low cardiac norepinephrine and elevated dopamine levels. However, myocardial catecholamine levels were normal (high norepinephrine, low dopamine) in 7 patients; both norepinephrine and dopamine were low in 6 patients; and norepinephrine levels were preserved but dopamine high in 7 patients. Cardiac norepinephrine level correlated only weakly with peripheral vascular resistance (r = 0.39, p less than 0.05), and examination of multiple other variables failed to reveal likely causes of the differences in cardiac norepinephrine and dopamine between patients. Thus, myocardial norepinephrine is not uniformly reduced in patients with severe CHF, and further attempts to delineate the factors regulating myocardial catecholamine concentration and adrenergic function in such patients are needed.