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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of standard-dose versus high-dose epinephrine on myocardial high-energy phosphates during ventricular fibrillation and closed-chest CPR.

STUDY OBJECTIVE: To evaluate the effects of standard-dose versus high-dose epinephrine on myocardial high-energy phosphate metabolism during resuscitation from cardiac arrest. DESIGN: Prospective, nonrandomized, controlled study using a swine model of cardiac arrest and resuscitation. INTERVENTIONS: After anesthesia, intravascular pressure instrumentation, and ten minutes of ventricular fibrillation arrest, closed-chest CPR was begun. After three minutes of CPR, animals were allocated to receive either 0.02 mg/kg i.v. standard-dose epinephrine (eight) or 0.2 mg/kg i.v. high-dose epinephrine (nine). The animals underwent thoracotomy and rapid-freezing transmural myocardial core biopsy for high-energy phosphate analysis 3.5 minutes after epinephrine administration. High-energy phosphate values were blindly determined using high-pressure liquid chromatography. RESULTS: Intravascular pressure (mm Hg) and high-energy phosphate (nmol/mg protein) results for standard-dose epinephrine versus high-dose epinephrine are, respectively, coronary perfusion pressure, 15.3 +/- 7.8 versus 23.7 +/- 5.5 (P = .0009); phosphocreatine, 0.4 +/- 0.8 versus 6.2 +/- 4.4 (P = .0003); adenosine triphosphate, 9.8 +/- 4.8 versus 12.7 +/- 5.7 (P = .30); adenosine diphosphate, 5.4 +/- 2.1 versus 6.1 +/- 1.3 (P = .41); and adenylate charge, 0.68 +/- 0.12 versus 0.72 +/- 0.12 (P = .87). CONCLUSION: High-dose epinephrine does not deplete myocardial high-energy phosphate when given in this model of prolonged ventricular fibrillation. High-dose epinephrine increases coronary perfusion pressure compared with standard-dose epinephrine. High-dose epinephrine administration repletes phosphocreatine during closed-chest CPR, thereby increasing myocardial energy stores.

Adenosine↗
PubMed1993

Increased aortic impedance precedes peripheral vasoconstriction at the early stage of ventricular failure in the paced canine model.

BACKGROUND: Aortic input impedance is altered in patients with congestive heart failure. However, little is known about whether this vascular response is an early change or a late manifestation of left ventricular dysfunction. METHODS AND RESULTS: This investigation used a paced canine model of congestive heart failure to demonstrate that abnormal aortic input impedance does evolve in the setting of ventricular systolic dysfunction and to prospectively define the time course of change in aortic input impedance and conduit vessel compliance. Studies were performed in closed-chest conditioned beagles aged 1 to 2 years that underwent hemodynamic evaluation at baseline and after induction of left ventricular dysfunction by rapid ventricular pacing. Within 48 hours of the onset of rapid ventricular pacing, we observed mild left ventricular systolic dysfunction with an echocardiographically derived left ventricular ejection fraction of 37% (p < .001 compared with baseline) measured during interruption of rapid ventricular pacing. Concomitant with this reduction in left ventricular systolic function, the aortic input impedance spectrum was shifted above baseline in all dogs studied. Characteristic impedance of the aorta significantly increased from 121 +/- 65 dynes.s/cm5 to 186 +/- 114 dynes.s/cm5 (P < .02), and a significant increase in the first modulus of impedance from 137 +/- 43 dynes.s/cm5 to 228 +/- 139 dynes.s/cm5 was observed (P < .05). Although characteristic aortic impedance increased by 50%, there was at this point no change in peripheral vascular resistance. Therefore, these abnormalities in aortic input impedance are representative of an early vascular change that evolves in response to ventricular systolic dysfunction. CONCLUSIONS: Considering the early appearance of these findings, the resultant impaired power transfer and reduced conduit vessel compliance likely contribute to the progression of abnormal myocardial energetics and systolic dysfunction characteristic of ventricular failure.

Animals↗
PubMed1993

Optimising ACE inhibitor therapy of congestive heart failure. Insights from pharmacodynamic studies.

Pharmacokinetic studies are often used to provide additional information regarding the use of pharmacological agents for the treatment of cardiovascular disorders. Pharmacokinetic data are available for the major angiotensin converting enzyme (ACE) inhibitors. However, practical guidelines regarding dosage and dosage intervals are not feasible, and measurements of serum drug concentrations are generally not useful in practice. Such use is obscured by the nature of enzymatic inhibition, renin and angiotensin I accumulation, the complex interaction of several organ systems, the compromise of organ system function due to the heart failure process, the effect of ACE inhibitors on other vasoactive substances and the cellular actions of carboxypeptidase (the enzyme otherwise known as ACE). Pharmacodynamic data demonstrate 2 important factors that influence ACE inhibitor pharmacokinetics and serum concentrations: the aging process and abnormal renal function. As most patients with moderate to severe heart failure have reduced renal function, this has practical implications. Furthermore, heart failure is common in the elderly, and even within the population with heart failure, a superimposed further reduction in renal function can be identified in elderly patients with heart failure. Therefore, a more careful analysis of ACE inhibitor dosage must be made in the presence of decreased renal function and in the elderly patient with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Management of refractory congestive heart failure.

Despite recent advances in the treatment of congestive heart failure (CHF), many patients continue to present with symptoms refractory to digoxin, diuretic, and vasodilatory therapy. Since it is unlikely that this population will decrease in the near future, practical approaches to management of refractory CHF are reviewed. Refractory CHF here is defined as New York Heart Association (NYHA) functional class III-IV heart failure, despite maximal drug therapy. Before such a diagnosis is made, the patient should be treated with digoxin, diuretics, and a vasodilator. Approach to therapy requires assessment of changing clinical status and pathophysiology, optimizing oral drug treatment, and providing temporary parenteral support when indicated. Specific attention should be given to factors that influence the optimal response to each of these 3 treatment classes. A theoretical, but unproven, concept suggests that combined vasodilatory therapy may be appropriate as long as excessive hypotension is avoided. In the course of management, a decision is required as to whether further optimization of therapy can be achieved on an outpatient basis. Hospital-based intravenous inotropic support given for 2-4 days will often provide the opportunity to restructure patient therapy.

Administration, Oral↗
PubMed1992

Maintenance of forearm vasodilator action of atrial natriuretic factor in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Infusions of atrial natriuretic factor (ANF) are frequently associated with attenuated natriuretic and diuretic responses in patients with congestive heart failure. However, ANF infusions result in systemic vasodilation, suggesting that end organ responsiveness to ANF may not be uniformly decreased. To determine if the vasodilator effects of ANF were altered in heart failure, strain-gauge plethysmography was utilized to measure forearm blood flow responses to the intraarterial infusion of ANF using a dose range that was low enough to avoid systemic effects. In 9 control subjects, ANF infusions of 0.5, 1.0, 2.0 and 4.0 micrograms/min/100 ml forearm volume significantly increased forearm blood flow from 3.21 +/- 1.71 to 5.69 +/- 3.14, 6.20 +/- 2.57, 6.64 +/- 2.53 and 6.97 +/- 2.49 ml/min/100 ml forearm volume, respectively (all p less than 0.01). In 7 patients with heart failure, ANF infusion significantly increased forearm blood flow from 2.19 +/- 0.98 to 3.18 +/- 1.70, 3.76 +/- 2.0 and 4.42 +/- 2.80 ml/min/100 ml forearm volume for the 0.5, 1.0 and 2.0 micrograms doses, respectively (all p less than 0.05). By analysis of variance, the forearm blood flow responses pooled over all doses were not significantly different between the 2 groups. At the 2.0 micrograms dose, the peak increase in forearm blood flow in normal subjects represented a 107% increase over baseline compared with a 102% increase in patients with heart failure. In summary, these data demonstrate that intraarterial administration of ANF in patients with heart failure resulted in dose-related increases in forearm blood flow. The responses were not significantly different from normal subjects expressed both as an absolute response and as a percent increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

The potential role of endothelin as a vasoconstrictor substance in congestive heart failure.

A rapidly growing body of data supports the concept of in situ regulation of vascular tone: the ability of vasoactive substances to regulate vascular tone at their site of production within the wall of the vasculature. Sufficient data exist to suggest that ineffective production or response to endothelium-dependent vasodilator substances, or excessive production or responsiveness to endothelium-dependent vasoconstrictor substances may play an important role in cardiovascular disorders such as hypertension, coronary artery spasm, restenosis following coronary angioplasty, and congestive heart failure. The present review summarizes data which support the concept that endothelin, a potent vasoconstrictor produced by the endothelium, may play a role in the excessive vasoconstriction of heart failure. Increased circulating plasma endothelin may be particularly relevant to the range of pulmonary vasoconstriction encountered in congestive heart failure, with a correlation revealing that the greatest increase of plasma endothelin occurs in patients with marked pulmonary hypertension within the congestive heart failure patients studied.

Animals↗
PubMed1992

Cardiac secretion of atrial natriuretic factor with exercise in chronic congestive heart failure patients.

We have previously reported a fivefold increase of plasma atrial natriuretic factor (ANF) in patients with congestive heart failure (CHF) compared with normal subjects. However, given the marked increase of ANF under basal conditions, the extent to which ANF secretion can further increase under physiological stress is not been clarified in CHF. We therefore evaluated ANF secretion during ergometric exercise in 11 patients with CHF, with peripheral venous ANF samples obtained at rest and peak exercise. In seven patients, simultaneous peripheral venous and right ventricular ANF samples were obtained to estimate myocardial ANF secretion. Hemodynamic characteristics of exercise included a significant increase of heart rate, mean arterial pressure, and cardiac output (all P < 0.01); reduction of systemic vascular resistance (P < 0.001); and increase of right atrial and pulmonary wedge pressures (P < 0.001). ANF was abnormally elevated at baseline (108 +/- 58 fmol/ml) yet increased further to 183 +/- 86 fmol/ml with exercise (P < 0.003). A step-up of right ventricular ANF, particularly during exercise, was consistent with active myocardial secretion, despite elevated baseline ANF levels.

Adult↗
PubMed1992

Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure.

BACKGROUND: Endothelin is a family of potent vasoconstrictor peptides of vascular endothelial origin. Although it has been proposed that the vasoconstrictor effects of endothelin are produced at the local vascular level, increased plasma concentration of endothelin has been identified in cardiovascular disorders. METHODS AND RESULTS: We tested whether immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma of congestive heart failure patients and whether levels correlated with hemodynamic characteristics. Twenty congestive heart failure patients (New York Heart Association class II-IV) were sampled in the morning after an overnight fast, before medication. Cardiac index was decreased to 2.14 +/- 0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg. The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61 mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13 pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals (3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically significant (p less than 0.0001). Endothelin-1 significantly correlated with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r = 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65, p less than 0.01). Endothelin-1 strongly correlated with the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r = 0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed the significance of these observations. CONCLUSIONS: Elevated immunoreactive endothelin-1 specifically correlated with the extent of pulmonary hypertension in congestive heart failure patients. Whether endothelin-1 is a regional mediator of pulmonary hypertension or a marker for its occurrence requires additional evaluation.

Adult↗
PubMed1991

Exercise-induced secretion of atrial natriuretic factor and its relation to hemodynamic and sympathetic stimulation in untreated essential hypertension.

This study evaluates the release of atrial natriuretic factor (ANF) during maximal exercise in 7 patients with untreated moderate to severe hypertension with invasive monitoring of hemodynamic characteristics in relation to sympathetic activity. Peripheral venous ANF (fmol/ml) was determined at rest and maximal exercise producing a respiratory exchange ratio of 1.14 +/- 0.10. In 5 of 7 patients, simultaneous right ventricular and peripheral venous ANF samples could be obtained to assess exercise myocardial secretion of ANF. With exercise, mean blood pressure increased from 150 +/- 26 to 192 +/- 29 mm Hg (p less than 0.001), pulmonary wedge pressure increased from 7 +/- 3 to 18 +/- 10 mm Hg (p less than 0.05) and ANF increased from 11.7 +/- 8.2 to 25.7 +/- 15.9 (p less than 0.02). This ANF response correlated weakly with pulmonary wedge pressure (r = 0.497, p = not significant), since patients without an increase in pulmonary wedge pressure had no increase in ANF. However, changes in pulmonary wedge pressure and plasma norepinephrine during exercise were inversely correlated (r = -0.811, p less than 0.02), with the greatest increase in norepinephrine occurring with a minimal increase in pulmonary wedge pressure. Similarly, ANF and plasma norepinephrine were inversely correlated during exercise (r = -0.869, p less than 0.05). A significant increase in right ventricular ANF indicated myocardial secretion. Plasma ANF therefore increased because of active myocardial production during exercise in patients with moderate to severe hypertension. These findings further suggest a directionally opposing relation between ANF release resulting from increased atrial tension and sympathetic nervous system influence on cardiac performance during exercise.

Adult↗
PubMed1991

Preserved atrial natriuretic peptide secretory function after cardiac transplantation.

The purpose of this investigation was to determine whether atrial natriuretic peptide (ANP) secretory function is preserved after cardiac transplantation. Thirteen hemodynamically stable outpatients performed supine exercise on a bicycle an average of 7 months after orthotopic cardiac transplantation. Right atrial pressure increased 2.2-fold (6 +/- 1 to 13 +/- 2 mm Hg) and pulmonary artery wedge pressure 2.1-fold (11 +/- 1 to 23 +/- 7 mm Hg) with exercise in the transplant recipients. Resting venous ANP level (114 +/- 19 pg/ml) and peak exercise venous level (373 +/- 61 pg/ml) was elevated in transplant recipients (p less than 0.001) compared with control subjects (21 +/- 1 and 92 +/- 14 pg/ml, respectively. This represents a 3.3-fold (114 +/- 19 to 373 +/- 61 pg/ml) increase in the ANP level from resting to exercise in transplant recipients and a 4.4-fold (21 +/- 1 to 92 +/- 14 pg/ml) increase in control subjects. A correlation between venous ANP levels and hemodynamics (right atrial pressure) was observed r = 0.49 p = 0.01. It is concluded that ANP levels at rest are elevated after cardiac transplant, the levels correlate with the intracardiac hemodynamics, and exercise-induced augmentation of plasma levels occurs.

Adult↗
PubMed1991

Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure.

Although enhanced sympathetic tone is a well recognized component of the autonomic profile characteristic of congestive heart failure, the contribution of parasympathetic withdrawal to this autonomic imbalance is less well described. The technique of spectral analysis of heart rate variability provides a dynamic map of sympathetic and parasympathetic tone and was thus used to define the nature of sympathetic-parasympathetic interactions in humans with idiopathic dilated cardiomyopathy and in a paced canine model of congestive heart failure. Humans with cardiomyopathy were found to have an augmentation of the sympathetically mediated low frequency area of the power density spectrum. Parasympathetic withdrawal was demonstrated by significant reductions in the parasympathetically mediated high frequency area (p less than 0.05) and the ratio of high to low frequency areas (p less than 0.01). Administration of atropine to normal subjects resulted in a significant reduction in the high frequency area (p less than 0.05) and the high/low frequency area ratio, both of which decreased within the range noted in patients with congestive heart failure. Administration of isoproterenol in normal subjects led to an augmentation of the low frequency area but to only a small decrease in the high/low frequency area ratio. Induction of congestive heart failure in a paced canine model resulted in alterations in the autonomic profile that resembled those seen in humans with ventricular failure. The prominent high frequency region of the spectrum at baseline, indicating a predominance of parasympathetic tone, was absent after the evolution of congestive heart failure, and there was a marked augmentation of the low frequency region of the spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pharmacology of angiotensin-converting enzyme inhibitors as a guide to their use in congestive heart failure.

The pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitors are difficult to assess for several reasons. First, these compounds exert their influence by inhibiting an intermediary enzyme of a cascade of enzymatic events, whose rate-limiting enzyme (renin) is not directly affected by ACE inhibition. Second, renin and angiotensin I accumulate during ACE inhibition and a change in the dose of an ACE inhibitor could produce sudden shifts of angiotensin I to angiotensin II. Third, components of the circulating renin system require the interaction of several organ systems and effector sites. Fourth, the kinetics of ACE inhibitors can be influenced by the organ systems responsible for drug absorption, metabolism and excretion, and the functional status of these systems can be affected by the heart failure process. Fifth, at least some portion of the cardiovascular effects of ACE inhibitors is influenced by the contributions of other systems whose physiologic effects may be of importance in some patients with congestive heart failure. Sixth, the potential impact of tissue-bound ACE is not yet fully understood. Finally, for appropriate drug dosing, the effects of aging on the heart failure process, the extent of renin system activity, and the disposition of ACE inhibitors need to be considered. Because of their complex pharmacokinetics, treatment with ACE inhibitors has been guided by their pharmacodynamic and clinical characteristics.

Age Factors↗
PubMed1990

Hemodynamic effects of oral nicorandil in congestive heart failure.

Twenty-five patients with congestive heart failure (CHF) underwent a double-blind randomized study of the acute hemodynamic effects of orally administered nicorandil, a newly developed vasodilator drug. A dose range of 10 to 60 mg was studied. Nicorandil, at a dose of 60 mg, caused statistically significant decreases in systemic systolic and diastolic blood pressure, right atrial pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance and systolic and diastolic pulmonary arterial pressure. A brief increase in cardiac index attributable to an increase in stroke volume without a change in heart rate was also observed. A dose of 40 mg produced similar results in cardiac index and systemic and pulmonary vascular resistance, but changes in other hemodynamic parameters were much smaller in magnitude and usually not of statistical significance. No significant hemodynamic response was seen to doses of 10 and 20 mg of nicorandil. Duration of action was short with nearly all hemodynamic parameters returning close to baseline within 3 hours. This rapid decrease in activity occurred in concert with a rapid plasma clearance of nicorandil as determined by serial measurements of plasma drug concentration. This study suggests that first-dose orally administered nicorandil elicits favorable, but brief, hemodynamic effects in CHF at doses greater than or equal to 40 mg.

Administration, Oral↗