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Biomedical subjects

M B Fowler

Publications and source records attributed to M B Fowler.

At least 19 recordsLinked to original sources
PubMed1992

Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group.

Patients with pulmonary hypertension are at risk of developing fatal right heart failure after heart transplantation. To evaluate this risk potential, candidates for heart transplantation are screened by measuring rest right heart pressures and the response to nitroprusside. To test the validity of this approach, the influence of pretransplantation right heart catheterization data on outcome after transplantation was analyzed in 293 of 301 consecutive patients. Patients with a pulmonary vascular resistance greater than 2.5 Wood units measured at baseline study had a 3-month mortality rate of 17.9% compared with 6.9% in patients with resistance less than or equal to 2.5 units (p less than 0.02). Patients with a pulmonary vascular resistance greater than 2.5 units at baseline study could be differentiated further according to their hemodynamic response to nitroprusside; those whose resistance could be reduced to less than or equal to 2.5 units with a stable systemic systolic pressure greater than or equal to 85 mm Hg had a 3-month mortality rate of only 3.8%. In contrast, patients whose pulmonary vascular resistance could not be reduced to less than 2.5 units, and those whose resistance could be reduced to less than or equal to 2.5 units but only at the expense of systemic hypotension (systolic pressure less than or equal to 85 mm Hg) had a 3-month mortality rate of 40.6% and 27.5%, respectively. Furthermore, all 10 patients who died of right heart failure belonged to the latter two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The influence of preoperative patient characteristics on early and late survival following cardiac transplantation.

In an attempt to identify the preoperative factors that influence survival following cardiac transplantation, we retrospectively analyzed multiple demographic, clinical, and hemodynamic data of 301 consecutive patients who underwent cardiac transplantation between December 1980 and July 1988 (cyclosporine era). Univariate and multivariate regression analyses revealed that the two most deleterious risk factors for premature death following transplantation were pulmonary hypertension not responsive to vasodilator challenge and preoperative requirement of hemodynamic support (intravenous inotropes or mechanical assistance). The combination of these two independent risk factors was an even stronger predictor of mortality (relative risk, 6:1; p less than 0.0001): the 3-month actuarial survival rate of the 20 patients with this combination was 30.3% versus 78.4% of the 47 patients with only pulmonary hypertension, 87.9% of the 42 patients with only the requirement of hemodynamic support, and 95.3% of the 172 patients with neither of these two risk factors. The difference in postoperative mortality between patients with versus those without these two risk factors is due to a higher rate of fatal infectious complications: six of 20 patients (30%) with both risk factors died from infection within 3 months after transplant compared with three deaths among 172 patients (1.7%) with neither of these risk factors. The majority of fatal infections were pulmonary. There were significantly more fatal and nonfatal infectious episodes in patients with one or both of these risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cardiac transplantation in patients with preexisting neoplastic diseases.

Cardiac transplantation has traditionally been reserved for individuals with end-stage congestive heart failure (CHF) in whom there is no history of other life-threatening systemic disorders. In most transplant centers, patients with a history of malignancy and severe heart failure have not been considered acceptable candidates for cardiac transplantation. In the last 4 years at Stanford University Medical Center, 8 cardiac transplants have been performed in 7 patients with a history of neoplastic disease. Six of these patients had already received treatment for lymphoproliferative disorders and in 1 case, a patient underwent a transplant after treatment for adenocarcinoma of the colon. Six of the 7 patients were discharged from the hospital and in that group, the 1-year posttransplant survival rate was 71%. This was comparable to an overall 1-year survival rate of 80% for patients undergoing a cardiac transplant at our center during the same period of time. At follow-up averaging over 2 years, there has been 1 case of recurrent neoplasia. One patient with evidence of radiation-induced pulmonary damage died of respiratory failure 2 days after transplantation. One patient required retransplantation because of intractable rejection and subsequently died from infectious complications. Immunosuppressive therapy in these patients has not been associated with an increased risk for neoplastic recurrence or for the development of posttransplant lymphoproliferative disorders. The current study demonstrates that in a carefully selected group, previously treated neoplastic disease should not represent a contraindication to cardiac transplantation.

Adolescent↗
PubMed1990

Cardiac adrenoceptors in the failing heart: effect of intervention.

The sympathetic nervous system is chronically activated in heart failure. This results in a reduction in numbers and sensitivity of beta-receptors, making the heart less responsive to the actions of catecholamines. This is specific to beta-receptors, the adenycyclase system being largely unaffected. Sympathomimetic agents are still used in patients with heart failure to augment cardiac contractility, but tachyphylaxis limits their long-term usefulness, and they may actually cause further myocardial damage. On the other hand, beta-blockade can improve sensitivity to catecholamines and cardiac action in some patients with severe left ventricular dysfunction, although this treatment can be hazardous and cannot yet be routinely recommended. Partial beta-agonists are theoretically useful since they can provide baseline sympathetic drive while protecting the heart against excessive sympathetic stimulation and down-regulation of beta-receptors. Xamoterol, a partial agonist with half the sympathetic activity of isoprenaline, has been shown to be superior to placebo and to digoxin in patients with mild to moderate heart failure.

Adrenergic beta-Agonists↗
PubMed1990

Selection of patients for cardiac transplantation.

In order to appropriately allocate the precious resource of donor organs for cardiac transplantation, one must adequately assess the prognosis of the prospective recipient with or without transplantation. This requires knowledge of the natural history of heart failure as well as those parameters by which it is evaluated. It also requires knowledge of those factors that make patients appropriate versus inappropriate surgical candidates. This article approaches both these necessary areas of patient evaluation.

Age Factors↗
PubMed1989

Frequency of familial nature of dilated cardiomyopathy and usefulness of cardiac transplantation in this subset.

A familial etiology was identified on the basis of family history in 16 (8.75%) of 184 patients undergoing cardiac transplantation at Stanford for endstage dilated cardiomyopathy (DC). These 16 patients, from 11 families, included 5 sibling pairs. To help determine optimal management of such patients, their case histories and posttransplant courses were reviewed. Mean age of patients at presentation was 23 +/- 15 years. In sibling pairs, duration of symptoms from onset to diagnosis was 14 +/- 5 weeks for the first sibling, but only 4 +/- 2 weeks for the second. Progressive cardiac enlargement was documented radiographically in siblings of transplant recipients in 2 families before the onset of symptoms. The posttransplant course with regard to rejection incidence, infectious complications, coronary artery disease and malignancy was similar to that of the 168 patients with nonfamilial DC. Actuarial survival at 5 years after transplantation was 80%. Thirteen patients (including all sibling pairs) are alive 1 to 11 years after transplantation. Sepsis was the cause of death in 3 patients, occurring during the early postoperative period in 2 and following retransplantation for graft atherosclerosis 7 years after the initial transplant in the third patient. Thus, diagnosis of DC in childhood or adolescence mandates evaluation and surveillance of family members, because this disease can progress rapidly. The favorable results of cardiac transplantation for familial DC suggest that it should be promptly considered for such patients with end-stage disease.

Adolescent↗
PubMed1989

Increased beta-receptor density and improved hemodynamic response to catecholamine stimulation during long-term metoprolol therapy in heart failure from dilated cardiomyopathy.

Severe heart failure is associated with a reduction in myocardial beta-adrenergic receptor density and an impaired contractile response to catecholamine stimulation. Metoprolol was administered during a 6-month period to 14 patients with dilated cardiomyopathy to examine its effects on these abnormalities. The mean daily dose of metoprolol for the group was 105 mg (range, 75-150 mg). Myocardial beta-receptor density, resting hemodynamic output, and peak left ventricular dP/dt response to dobutamine infusions were compared in 9, 14, and 7 patients, respectively, before and after 6 months of metoprolol therapy while the patients were on therapy. The second hemodynamic study was performed 1-2 hours after the morning dose of metoprolol had been given. Myocardial beta-receptor density increased from 39 +/- 7 to 80 +/- 12 fmol/mg (p less than 0.05). Resting hemodynamic output showed a rise in stroke work index from 27 +/- 4 to 43 +/- 3 g/m/m2, p less than 0.05, and ejection fraction rose from 0.26 +/- 0.03 to 0.39 +/- 0.03 after 6 months of metoprolol therapy, p less than 0.05. Before metoprolol therapy, dobutamine caused a 21 +/- 4% increase in peak positive left ventricular dP/dt; during metoprolol therapy, the same dobutamine infusion rate increased peak positive dP/dt by 74 +/- 18% (p less than 0.05). Thus, long-term metoprolol therapy is associated with an increase in myocardial beta-receptor density, significant improvement in resting hemodynamic output, and improved contractile response to catecholamine stimulation. These changes indicate a restoration of beta-adrenergic sensitivity associated with metoprolol therapy, possibly related to the observed up-regulation of beta-adrenergic receptors.

Cardiomyopathy, Dilated↗
PubMed1988

Hemodynamic, renal and endocrine effects of atrial natriuretic peptide infusion in severe heart failure.

The cardiac release and total body and renal clearances and the hemodynamic, renal and endocrine effects of increasing doses of atrial natriuretic peptide were investigated in 12 patients with severe chronic congestive heart failure. Immunoreactive arterial plasma levels of atrial natriuretic peptide were 10-fold higher than normal and there was no correlation between aortic atrial natriuretic peptide and cardiac filling pressures. The heart released atrial natriuretic peptide into the coronary sinus. The kidney, though a major clearance site, accounted for only 33% of the total body clearance. Administration of 0.3 micrograms/kg per min atrial natriuretic peptide produced significant changes in heart rate (95 +/- 4 to 85 +/- 4 beats/min) and mean arterial (92 +/- 8 to 77 +/- 9 mm Hg), right atrial (13 +/- 3 to 8 +/- 2 mm Hg) and mean pulmonary artery occluded (27 +/- 3 to 14 +/- 3 mm Hg) pressures. Atrial natriuretic peptide increased cardiac index (2.25 +/- 0.18 to 2.83 +/- 0.3 liters/min per m2) and stroke work index (21 +/- 1.5 to 29 +/- 3.4 g/m2), whereas systemic vascular resistance (1,424 +/- 139 to 1,033 +/- 97 dynes.s.cm(-5)) decreased. Infusion of 0.1 microgram/kg per min atrial natriuretic peptide increased urinary flow 128%, fractional excretion of sodium 133% and fractional excretion of potassium 35%. The filtration fraction increased from 29 +/- 2 to 31 +/- 4%. This represented a disproportionate rise in glomerular filtration rate over renal plasma flow. Plasma aldosterone and norepinephrine decreased whereas plasma renin activity remained unchanged. In association with these hemodynamic, excretory and endocrine changes, the urinary excretion of cyclic guanosine monophosphate doubled. Placebo had no effect. These results showed that, despite high circulating levels of atrial natriuretic peptide, administration of this hormone in heart failure is associated with potentially beneficial hemodynamic, renal and endocrine effects.

Adult↗
PubMed1988

Effect of preoperative hemodynamic support on survival after cardiac transplantation.

The accessibility and success of cardiac transplantation promotes transplantation for a broad range of recipients, including those requiring intravenous inotropes or mechanical-assist devices. To determine if survival is dependent on preoperative requirements for hemodynamic support, we studied 230 patients who underwent transplant at the Loyola, Stanford, and UTAH programs from December 1, 1984 through November 30, 1986, and who were followed up for 34 months postoperatively. Group 1 (n = 132 of 230, 57%) patients required only oral medical therapy to maintain hemodynamic compensation; Group 2 (n = 69 of 230, 30%) patients were dependent on intravenous inotropic support; and Group 3 (n = 29 of 230, 13%) patients required mechanical assistance. Pretransplant characteristics showed that dilated cardiomyopathy was more common in Group 2 patients, and lower cardiac index and ejection fraction were more prevalent in Group 3 patients as expected. Although survival was lower in Group 3 only at 1 month (Group 1, 98.5%; Group 2, 92.8%; and Group 3, 86.2%; p less than 0.01), the survival advantage in Groups 1 and 2 was lost by 3 months, with 1-year survival rates of 88.6% in Group 1, 81.2% in Group 2, and 82.8% in Group 3. Allograft survival and cause of death were not different among the three groups. Acute rejection occurred at a lower monthly frequency in the first 4 months in Group 3 (Group 1, 0.47 +/- 0.03; Group 2, 0.47 +/- 0.05; and Group 3, 0.29 +/- 0.06; p less than 0.01), whereas infectious complications occurred at similar frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Assisted Circulation↗
PubMed1987

Poor survival of patients with idiopathic cardiomyopathy considered too well for transplantation.

Although the success of cardiac transplantation has encouraged earlier referral of potential candidates, those with mild symptoms of heart failure are frequently considered "too well" for transplantation. Outcome was investigated for 28 patients with non-ischemic dilated cardiomyopathy and ejection fraction of 25 percent or less who were denied transplantation due to lack of severe symptoms. One-year survival without transplantation was 46 percent. Low stroke volume and history of ventricular arrhythmias were independent predictors of early mortality. High risk, defined as either stroke volume of 40 ml or less or history of ventricular arrhythmia, identified 13 of 14 patients who did not survive one year and only one of 12 one-year survivors (p less than 0.001). Low stroke volume predicted hemodynamic failure (p less than 0.05) whereas arrhythmic history predicted sudden death (p less than 0.001). Clinical status improved in only six patients, all of whom had symptom duration of seven or less months at initial evaluation (p less than 0.001). Thus, patients referred to transplantation for dilated cardiomyopathy with an ejection fraction of 25 percent or less have a poor prognosis even if symptoms are mild. Patients with high hemodynamic risk may require early transplantation, whereas those with high arrhythmia risk may require other aggressive therapy in order to avoid transplantation until symptoms become severe.

Cardiomyopathy, Dilated↗
PubMed1987

Hypoxic pulmonary vasoconstriction persists in the human transplanted lung.

The preservation of hypoxic pulmonary vasoconstriction (HPV) in the denervated lung was studied in five human heart-lung transplant recipients. All five patients showed significant increases in mean pulmonary artery pressure and pulmonary vascular resistance during hypoxic exposure, returning toward normoxic values during recovery. Aside from PAO2 and Pao2, other factors known to influence pulmonary vascular resistance did not change significantly during the hypoxic period. There was no relation between the length of the post-transplantation period and the intensity of HPV, suggesting that reinnervation of the pulmonary vascular bed did not account for persistent HPV and that HPV persists in the human transplanted lung despite the loss of autonomic neural innervation.

Adult↗
PubMed1987

Changes in Doppler echocardiographic indexes of left ventricular function as potential markers of acute cardiac rejection.

Changes in left ventricular filling and ejection as potential markers of cardiac allograft rejection were evaluated by serial Doppler echocardiography performed in 23 normal volunteers and within 24 hr of endomyocardial biopsy in 22 patients aged 14 to 53 years (mean 37). Peak aortic velocity, left ventricular ejection time index (ETI), isovolumic relaxation time (IVRT), mitral valve pressure half-time (PHT), peak early mitral flow velocity (M1), and velocity following donor atrial systole (M2) were measured without prior knowledge of endomyocardial biopsy findings. Biopsy specimens were graded histologically as: no rejection, mild rejection (cellular infiltrate), and moderate rejection (myocyte necrosis). A total of 120 biopsy-correlated Doppler echocardiographic studies were performed during 16 weeks after cardiac transplantation. Heart rate and mean arterial pressure were significantly higher in transplant recipients than in normal subjects. IVRT and PHT were significantly longer, while M1 and M2 were similar. Peak aortic velocity was higher in normal subjects than in transplant recipients, while ejection time was similar. Rejection of increasing severity was associated with a progressive shortening of IVRT and PHT and with an increase in M1 (p less than .0005 for all comparisons). Peak aortic velocity and ejection time index did not change significantly with rejection. These data indicate that acute cardiac rejection is accompanied by alteration in left ventricular filling dynamics detectable by Doppler echocardiography, without measureable changes in systolic function. These changes may provide noninvasive markers for surveillance of rejection.

Acute Disease↗
PubMed1986

Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response.

We developed methods for identifying beta-adrenergic receptors in human right ventricular endomyocardial biopsy tissue with the radioligand (-)[125I]iodocyanopindolol (ICYP). Specific ICYP binding in a crude, high-yield membrane preparation derived from endomyocardial biopsy tissue was high (specificity greater than 90%), of high affinity (KD around 20 pM), saturable and stereospecific for the (-) vs the (+) isomer of isoproterenol. Subjects with mild-moderate and severe biventricular dysfunction had respective decreases in beta-adrenergic receptor density of 38.2% and 57.7% when normalization methods were averaged, with no significant differences in ICYP dissociation constant. A subgroup of subjects was subdivided by left ventricular ejection fraction (LVEF) into those with mild cardiac dysfunction (LVEF less than 0.50 greater than 0.40) and severe heart failure (LVEF less than 0.20) and given graded sequential infusions of dobutamine and calcium gluconate. Those with severe cardiac dysfunction had marked impairment of the dobutamine dP/dt and stroke work index response, whereas these responses to calcium did not differ in the two groups. These data indicate that in the intact human heart endomyocardial biopsy may be used for direct analysis of beta-adrenergic receptors, heart failure-associated myocardial beta-adrenergic down-regulation begins with mild-moderate ventricular dysfunction, reduction in myocardial beta-receptor density is related to degree of heart failure, and beta-receptor down-regulation is associated with pharmacologically specific impairment of the beta-agonist-mediated contractile response.

Adult↗
PubMed1985

Rationale for beta-adrenergic blocking drugs in cardiomyopathy.

Activation of the sympathetic nervous system has traditionally been regarded as an important compensatory mechanism that helps to maintain myocardial contractility in severe heart failure. Recent findings suggest that increased catecholamine levels are linked to decreased beta-adrenergic receptor density and myocardial damage. Thus, rather than aiding the failing heart, increased myocardial exposure to catecholamines may actually contribute to further deterioration in myocardial function. Beta-adrenergic blocking drugs may ameliorate these harmful effects and paradoxically result in improved ventricular performance.

Adrenergic beta-Antagonists↗
PubMed1985

Beta-adrenergic function in heart muscle disease and heart failure.

Using data derived from clinical and experimental observations, we examine the role of the myocardial beta-adrenergic receptor system in pathophysiologic processes involved in heart muscle disease and heart failure. The available data suggest that the sympathetic nervous system exerts important influences on myocardial structure and function. As such the beta-adrenergic pathways represents an obvious locus for therapeutic intervention in evolving cardiomyopathic states.

Adenylyl Cyclases↗