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Biomedical subjects

G L Pierpont

Publications and source records attributed to G L Pierpont.

At least 19 recordsLinked to original sources
PubMed1999

Regulation of myocardial blood flow by oxygen consumption is maintained in the failing heart during exercise.

The hemodynamic abnormalities and neurohumoral activation that accompany congestive heart failure (CHF) might be expected to impair the increase in coronary blood flow that occurs during exercise. This study was performed to determine the effects of CHF on myocardial oxygen consumption and coronary blood flow during exercise. Coronary blood flow was measured in chronically instrumented dogs at rest, during 2 stages of graded treadmill exercise under control conditions (n=10), and after the development of CHF produced by 3 weeks of rapid ventricular pacing (n=9). In the normal dogs, coronary blood flow increased during exercise in proportion to the increase in the heart rate x the left ventricular systolic blood pressure product (RPP). After the development of CHF, resting myocardial blood flow was 25% lower than normal (P<0.05). Myocardial blood flow increased during the first stage of exercise, but then failed to increase further during the second stage of exercise despite an additional increase in the RPP. Myocardial oxygen consumption during exercise was significantly lower in animals with CHF and paralleled coronary flow. Despite the lower values for coronary blood flow in animals with CHF, there was no evidence for myocardial ischemia. Thus, even during the second level of exercise when coronary flow failed to increase, myocardial lactate consumption continued and coronary venous pH did not fall. In addition, the failure of coronary flow to increase as the exercise level was increased from stage 1 to stage 2 was not associated with a further increase in myocardial oxygen extraction. Thus, cardiac failure was associated with decreased myocardial oxygen consumption and failure of oxygen consumption to increase with an increase in the level of exercise. This abnormality did not appear to result from inadequate oxygen availability, but more likely represented a reduction of myocardial oxygen usage with a secondary decrease in metabolic coronary vasodilation.

Animals↗
PubMed1999

Physician risk assessment and APACHE scores in cardiac care units.

BACKGROUND: The need to correct outcome data for case mix is well recognized, but risk assessment for coronary care unit (CCU) patients remains problematic. HYPOTHESIS: This study determined the feasibility of using physicians' opinions to predict mortality for CCU patients and compared their results to Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. METHODS: A prospective observational study was performed on consecutive patients admitted to a university-affiliated Veterans Affairs Medical Center CCU over a 2-month period. Physician assessment of likely mortality during hospitalization, obtained using an MD Prognosis Score ranging from 1 (best) to 7 (worst), was compared with APACHE II scores. RESULTS: MD Prognosis Scores were obtained on 122 of the 237 eligible patients (51% response rate) and averaged 2.3 +/- 1.4 (mean +/- standard deviation). APACHE II scores on these patients averaged 9.9 +/- 4.8 (range 2-29) with very poor correlation between the two methods (r = 0.3). Of the four patients who died, three had MD prognosis scores of 7. None of the survivors had scores of 7 and only three had scores of 6. APACHE II did not predict a high likelihood that any of the patients would die (none with > 90% likelihood of mortality). CONCLUSIONS: APACHE scores are inadequate for cardiac patients. Although physicians can identify CCU patients most likely to die, reliance on physician scoring systems is limited by difficulties in obtaining their opinion. A new method of risk assessment for acutely ill cardiac patients is needed if CCU outcomes are to be compared across institutions.

APACHE↗
PubMed1997

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).

Animals↗
PubMed1996

A point mutation in the cytb gene of cardiac mtDNA associated with complex III deficiency in ischemic cardiomyopathy.

We report a high incidence of reduced respiratory Complex III activity in heart muscle concomitant with the presence of a specific mutation in cytochrome b (cytb) in patients with ischemic cardiomyopathy. This C-->A mutation at nt 15452 converts the 236th residue of cytb from a leucine to isoleucine, is heteroplasmic and was observed in only 2 of 43 controls. Complex III activity is reduced (> 50%) in 5 of 6 patients with the C-->A15452 mutation suggesting that the cytb mutation is responsible for decreased Complex III activity and may play a role in the pathophysiology of ischemic cardiomyopathy.

Adult↗
PubMed1995

Effect of computerized charting on nursing activity in intensive care.

OBJECTIVE: To measure the impact on nursing activity of introducing computerized medical records into intensive care units (ICUs). DESIGN: Prospective data collection monitoring the activity of ICU nurses before and after installation of a computerized charting system. SETTING: A six-bed coronary care unit and an eight-bed medical ICU at the Minneapolis VA Medical Center. SUBJECTS: Registered nurses providing intensive care services. INTERVENTIONS: Installation of a Clinical Information System that computerized the ICU medical records. MEASUREMENTS AND MAIN RESULTS: Before computer installation, nurses spent 24% of their time manipulating data (7% gathering and 17% charting). After installation, charting time decreased to 10%, and data gathering time decreased to 4%, while 10% of time was spent at computer terminals entering or reviewing data. The total time manipulating data post-installation was thus 24% (i.e., unchanged from previous). Computerized charting did not alter time spent in patients' rooms (43% pre- and 43% postinstallation) compared with time spent at the central station (37% pre- and 36% post-installation) or elsewhere (20% pre- and 21% postinstallation). Relative time spent at various tasks varied between units and from shift to shift, but the net effect of computerized charting was that nurses had more time available at the central station for monitoring, and that the computer terminals were used primarily in the patient rooms. CONCLUSIONS: Computerized charting will not necessarily provide ICU nurses with a net excess of time for tasks unrelated to manipulating data.

Computer Terminals↗
PubMed1992

Catecholamines in turkeys with alcohol-induced cardiomyopathy.

Although alcoholic cardiomyopathy has been difficult to reproduce in animals, turkeys fed 5% ethanol develop a dilated congestive cardiomyopathy. We therefore used this model to examine the adrenergic response to left ventricular dysfunction induced by alcohol. In normal turkeys, norepinephrine in kidneys decreased markedly with age from 1 day to 2 mo, with a similar but less dramatic decrease in cardiac norepinephrine. By 2 mo, chronic alcohol ingestion depleted cardiac norepinephrine compared with controls (217 +/- 22 vs. 316 +/- 41 ng/g, P < 0.05), even though cardiac norepinephrine is relatively low in turkeys compared with many other animals and humans. Norepinephrine in aorta was also decreased with alcohol administration, but kidney norepinephrine was unaffected. Dopamine was unaltered in any of the organs studied. Plasma norepinephrine is normally high in turkeys with arterial levels greater than venous (2,898 +/- 746 vs. 1,987 +/- 531 pg/ml at 2 mo). Venous plasma norepinephrine did not differ from control (2,595 +/- 547 pg/ml) after 2 mo of alcohol. Thus, as in humans, cardiomyopathy in alcohol-fed turkeys is associated with reduced cardiac norepinephrine, but unlike humans with cardiomyopathy, circulating norepinephrine remains normal.

Aging↗
PubMed1989

Myocardial carnitine in end-stage congestive heart failure.

To test the hypothesis that carnitine is decreased in the myocardial tissue of patients with end-stage congestive heart failure (CHF), left ventricular myocardial carnitine was measured in 51 patients undergoing orthotopic cardiac transplantation. The study group included patients with idiopathic dilated cardiomyopathy, coronary artery disease, myocarditis and rheumatic heart disease. Myocardial carnitine varied in different cardiac chambers. In normal control hearts, the left and right ventricular total carnitine was similar, but the ventricles had higher levels than the atria (p less than 0.005); in 30 hearts in CHF, the left ventricular total carnitine was higher than in the right ventricle (p less than 0.001) and both ventricles had higher total carnitine than the atria (p less than 0.005). Only 7 of 51 patients with CHF had low myocardial carnitine, whereas plasma carnitine was elevated in all diagnostic groups of end-stage CHF studied.

Adolescent↗
PubMed1988

Pathophysiology of congestive heart failure secondary to congestive and ischemic cardiomyopathy.

Dilated cardiomyopathy, owing to any cause, usually culminates in the clinical syndrome of congestive heart failure. Heart failure is characterized by exertional dyspnea and fatigue, but the precise mechanisms that produce these symptoms are still not clear. Sodium retention occurs early in heart failure, but this disturbance is dynamic in nature and is not always present in the patient. The mechanism of early salt and water retention in heart failure is not defined. Gross edema and ascites occur much later, undoubtedly owing to the convergence of a number of factors. The peripheral adaptations to heart failure include activation of the renin-angiotensin system and the sympathetic nervous system, and the release of AVP. The result is an increase in preload with a resultant increase in stroke volume for some patients, but the price is paid in the form of heightened impedance to ejection and circulatory congestion. The sympathetic nervous system disturbances in heart failure are striking, as disturbances in both circulating and myocardial NE levels are consistently found. Vasorelaxant and natriuretic hormones, as well as certain prostaglandins, may be released in an attempt to offset excessive "compensatory" pressor-sodium retentive mechanisms, but the net result seems to be excessive peripheral vasoconstriction and a downward spiral of deterioration in many patients. One would hope that an unraveling of the complex pathophysiology of heart failure would lead to therapy that would change the natural history of the disease. The results of the first V-HeFT trial give room for cautious optimism in this regard.

Cardiomyopathy, Dilated↗
PubMed1987

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.

Adult↗
PubMed1987

Hemodynamic and regional blood flow response to piroximone (MDL 19,205) in dogs with congestive heart failure: a comparison with dobutamine.

This study compares the effects of piroximone (MDL 19,205), a new inotropic agent, with dobutamine in dogs with congestive heart failure. With dobutamine, (15 micrograms/kg/min) left ventricular (LV) dp/dt increased from 2220 +/- 215 (mean +/- S.E.M.) to 2815 +/- 280 mm Hg/sec and cardiac index increased from 2.9 +/- 0.2 to 3.7 +/- 0.4 liters/min/m2, whereas LV filling pressure was essentially unchanged (18.7 +/- 2.6-16.3 +/- 2.4 mm Hg). The hemodynamic effects of piroximone (50 micrograms/kg/min) were more pronounced. LV dp/dt increased from 2615 +/- 260 to 3760 +/- 410 mm Hg/sec and cardiac index from 3.0 +/- 0.1 to 4.4 +/- 0.6 liters/min/m2, whereas LV filling pressure decreased from 15.6 +/- 2.4 to 6.4 +/- 1.8 mm Hg (all P less than .05). Systemic vascular resistance index decreased from 2730 +/- 225 to 1905 +/- 256 dynes sec cm-5 m-2. Regional blood flow to the myocardium increased 48% with dobutamine and 24% with piroximone, whereas skeletal muscle flow increased 59% with dobutamine and 36% with piroximone. Renal blood flow remained unchanged with either drug. We conclude that piroximone is an inotropic agent with vasodilator properties that has an interesting hemodynamic profile somewhat similar to that of dobutamine but with the advantage of being orally active; therefore piroximone could be useful in the treatment of heart failure.

Animals↗
PubMed1985

Intra-arterial monitoring during cardiopulmonary resuscitation.

Because arterial cannulation assists in management of critically ill patients (pts), we assessed the utility of extending intra-arterial monitoring to hospitalized patients suffering in-hospital cardiopulmonary arrest outside of intensive care wards. A totally self-contained, readily portable system for rapid insertion of emergency intra-arterial lines was evaluated in 16 pts from 53 to 89 years old (mean = 66.5 years) undergoing cardiopulmonary resuscitation. Cannulation was successful in 14 pts (88% success rate). In 8 of 14 pts, cannulation was achieved rapidly and efficiently, whereas in six it was slightly delayed, once due to technical problems and five times due to difficulty cannulating the vessel. In addition to providing continuous pressure monitoring and ready access to arterial blood samples, direct feedback from the intra-arterial pressure waveform frequently led to improved compression technique by the resuscitator performing external cardiac massage. We conclude that under selected circumstances emergency intra-arterial monitoring has a potentially important adjuvant role during cardiopulmonary resuscitation.

Aged↗
PubMed1985

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.

Acidosis↗
PubMed1985

Practical problems in assessing risk for coronary artery bypass grafting.

In order to put results of a surgical program in proper prospective, risk factors for the population being treated should be carefully assessed. This paper discusses the practical problems involved in determining the risk of surgical mortality for patients undergoing isolated coronary artery bypass grafting. A risk equation developed by the Collaborative Study in Coronary Artery Bypass was applied to a veterans hospital population. A simplified method of determining left ventricular function from clinical angiography reports was found to be a reasonable substitute for the more complex left ventricular scoring system used by the collaborative study. Results showed the veterans group to be at increased risk, primarily due to an older average age and higher incidence of left ventricular dysfunction.

Adult↗
PubMed1985

Ventricular myocardial catecholamines in primates.

We report myocardial catecholamine levels in primate ventricles assayed by high-pressure liquid chromatography with electrochemical detection. The norepinephrine content of the left ventricles of 11 monkeys (four rhesus and seven cynomolgus) was 1391 +/- 362 ng/gm (+/-SD) with a definite gradient from base (highest) to apex (lowest concentration). Dopamine and epinephrine were present in much lower concentrations (51.8 +/- 24.5 ng/gm and 59.2 +/- 20.0 ng/gm, respectively), but were similarly distributed throughout the left ventricle. There was considerable variation in norepinephrine concentration between animals, but the dopamine/norepinephrine ratio was very consistent within a given animal, averaging 3.7% +/- 1.4%. These values are probably indicative of what normal concentrations of catecholamines are likely to be in humans, and provide a basis for interpretation of results obtained in disease studies.

Animals↗
PubMed1984

"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)

Aged↗
PubMed1984

Regional differences in adrenergic function within the left ventricle.

Since ischemic heart disease (IHD) is inhomogeneous, the adrenergic response of the heart to ischemia or infarction could depend on the level of adrenergic supply within specific regions of the myocardium. Therefore we quantified myocardial norepinephrine (NE) content of tissue samples from 54 different sites in the left ventricle (LV) of four normal dogs using high-pressure liquid chromatography with electrochemical detection. Up to 10-fold differences in NE content occurred within a single LV. The NE distribution followed a consistent pattern, demonstrating a gradient from apex (avg minimum value of 162 ng/g of tissue) to base (avg maximum value 844 ng/g). No epicardial-to-endocardial gradient was present. In six other dogs a similar pattern was found in myocardial uptake of radioactively labeled NE and epinephrine assessed 2 min after intravenous injection. These results suggest that areas of high tissue NE represent regions rich in adrenergic supply and high in adrenergic activity, not merely NE stored in inactive pools. Samples from a human autopsy specimen suggest that these findings can be extrapolated to humans.

Animals↗
PubMed1984

Quantitative analysis of postmortem changes in myocardial norepinephrine using HPLC with electrochemical detection.

Myocardial adrenergic function may be important in the pathophysiology of many cardiac abnormalities, and quantitative analysis of catecholamines in cardiac tissue can provide insight in the role of adrenergic neurons in specific disorders. Our purpose was to determine the stability of myocardial catecholamines postmortem to assess the validity of using postmortem samples to represent premorbid conditions and to provide information applicable to proper handling of biopsy specimens. Serial myocardial samples were obtained postmortem in rats and dogs for which norepinephrine and dopamine levels were analyzed using high-pressure liquid chromatography with electrochemical detection. No significant differences in catecholamine content were found between samples taken immediately after death and those taken 15 minutes later. Thereafter, a progressive decline in catecholamines was observed. We conclude that biopsy or postmortem samples frozen within 15 minutes of death will accurately reflect premortem catecholamine values.

Animals↗