Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES: The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND: Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS: Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS: The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS: This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.     

Clinical and hemodynamic criteria for use of the intra-aortic balloon pump in patients requiring cardiac surgery

In order to establish criteria for elective use of the intra-aortic balloon pump (IABP) in patients having cardiac surgery, we conducted a retrospective study of 43 patients who required counterpulsation, because of inability to be weaned from cardiopulmonary bypass, between May, 1972, and June, 1974. Patients in cardiogenic shock preoperatively were excluded. The 43 patients included 23 (Group A) who had severe preoperative left ventricular dysfunction with a mean cardiac index less than 1.8 L. per minute per square meter, ejection fraction less than 30 per cent, and end-diastolic pressure greater than 22 mm. Hg; 20 patients (Group B) had a combination of moderate cardiac dysfunction (cardiac index less than 2.2, ejection fraction less than 40, end-diastolic pressure less than 18) in the presence of acute infarction or severe aortic stenosis (gradient greater than 80 mm. Hg) with or without coronary disease. An inverse relationship was noted between survival and delay from completion of operation to the use of 1ABP. Thirty-two of 43 patients were weaned off bypass and were balloon assisted for 12 to 96 hours postoperatively; 25 patients were discharged (58 per cent). In Subgroup A, 14 of 23 (60 per cent) and, in Subgroup B, 9 of 20 (45 per cent) were long-term survivors. Based on these findings, 45 patients were operated upon between June, 1974, and December, 1975, with elective use of 1ABP and were assessed by serial hemodynamic studies. Sixteen had severe preoperative left ventricular dysfunction similar to Subgroup A and 29 had moderate dysfunction in combination with pathology similar to Subgroup B. Fifteen of these patients were hemodynamically unstable at time of arrival in the operating room; 1ABP was inserted under local anesthesia. Thirty-nine patients (87 per cent) were weaned off bypass and were hospital survivors. In Subgroup A, 13 of 16 (81 per cent) and, in Group B, 21 of 29 (72 per cent) were long-term survivors. Criteria for elective use of 1ABP in cardiac surgery should include severe preoperative left ventricular dysfunction or a combination of moderate dysfunction with coronary or valvular pathology. Elective 1ABP improves the survival with trivial iatrogenic morbidity.     

Stress test in the elderly. Clinical, hemodynamic, metabolic and electrocardiographic variables]

Pentylenetetrazol is a convulsive drug acting on gamma-aminobutyric acid-A (GABA[A]) gated-chloride receptors. In this study we used a subconvulsive dose (30 mg/kg) of pentylenetetrazol to induce a fully kindled state in rats. Glutamate receptors were evaluated using [3H]-[1(2-thienylcyclohexyl)]-piperidin (TCP) and [3H]kainate receptor autoradiography and [3H]muscimol autoradiography was used to study GABA(A) receptors. In fully kindled rats decreased N-methyl-D-aspartate receptor binding was found in parietal cortex, area CA2 of hippocampus and piriform cortex. Decreased kainate receptor binding was observed in all areas of the hippocampus, the medial amygdala and in the piriform cortex in the kindled rats. In contrast, GABA(A) receptor binding increased in the dentate gyrus. It is concluded that modulatory neuronal plasticity events are induced in fully pentylenetetrazol kindled rats, which appears to lead to decreased glutamatergic excitation and increased GABAergic inhibition in brain regions implicated in the development of seizure activity.     

Cardiovascular effects of a new inotropic agent, U. K. 14275, in patients with coronary heart disease

1 The chronotropic and inotropic properties of U.K. 14275, a phosphodiesterase inhibitor were assessed in patients with coronary heart disease. 2 Left ventricular function was assessed in eight patients with acute myocardial infarction using the non-invasive measurement of systolic time intervals. 3 Twelve patients with angina pectoris were studied during diagnostic coronary arteriography. Left ventricular function was assessed using a high fidelity catheter tipped transducer in the left ventricle. 4 In both groups of patients U.K. 14275 infused intravenously in doses of 32, 64, 128 and 256 microgram kg-1 bodyweight min-1 enhanced the contractile state of the left ventricle without altering the heart rate.     

Central haemodynamic and forearm vascular effects of morphine in patients after open heart surgery

Central haemodynamic and forearm vascular changes following administration of morphine i.v. were studied in patients 24--30 h after open heart surgery. Right atrial pressure, heart rate, mean arterial pressure, cardiac output and stroke volume were measured before and after morphine 5 and 10 mg per 70 kg in 14 subjects. In a further group of eight subjects, forearm blood flow was measured after morphine 10 mg per 70 kg. Total systemic and forearm vascular resistance were derived from these measurements. In spite of wide individual variations, significant decreases in mean arterial pressure occurred in most of the patients and appeared to be dose related. Significant decreases in mean cardiac index were noted only after morphine 10 mg per 70 kg. Forearm blood flow increased consistently and significantly and there was a corresponding decrease in vascular resistance. The decrease in mean arterial pressure and the change in forearm vascular resistance indicated that vasodilatation was probably the principle cause of the decrease in arterial pressure, whereas the sustained decrease in cardiac output seemed to indicate an effect on venous capacitance. The predominant action of morphine appears to be peripheral, causing a decrease in vascular resistance and, possibly, an increase in venous capacitance.     

Platelet-aggregation inhibition and hemodynamic effects of beraprost sodium, a new oral prostacyclin derivative: a study in healthy male subjects

The antiaggregation and hemodynamic effects of the new prostacyclin analogue beraprost sodium were investigated in a randomized, placebo-controlled, double-blind clinical trial of Latin-square design. Twelve healthy Caucasian males randomly received 8-day oral treatments of 20, 40, and 60 micrograms of beraprost sodium and a placebo. One-week washout periods followed each treatment. Pharmacokinetic and pharmacodynamic measurements were performed on days 1 and 8 for each period of treatment. All three doses of beraprost sodium significantly inhibited platelet aggregation on day 8 (compared with placebo) during the 1st h after drug intake. Incubation of the 60-micrograms beraprost sodium samples with ADP (2, 5, and 10 microM) and collagen (1.25 micrograms/mL) decreased platelet aggregation by 10, 19, 16, and 6 +/- 4% (mean +/- SE), respectively, compared with placebo. No significant hemodynamic effects on blood pressure, heart rate, and digital pulse were observed. The 60-micrograms dose of beraprost sodium did significantly decrease the IRZ index (which may reflect the left ventricular pre-ejection period) on days 1 and 8. Some subjects experienced headache and facial flushing, effects that were dose dependent and reversible. Beraprost sodium at 20- to 60-micrograms doses exerts platelet antiaggregation (day 8 of therapy) and slight hemodynamic (days 1 and 8 of treatment) effects in Caucasian males. Beraprost sodium hemodynamic effects and potential benefits in patients with cardiovascular disease should be explored further.     

Adverse effects of a new non-ionic contrast medium in heart catheterization

Tolerance of a New Non-ionic Contrast Medium during Heart Catheterization The new non-ionic contrast medium iomeprol (CAS 78649-41-9) was investigated for adverse reactions and diagnostic quality in 75 patients undergoing heart catheterization. Blood pressure and ECG were continuously registered. The patients were asked for subjective complaints by using a standardized questionnaire. Experienced cardiologists assessed the diagnostic quality of the angiograms. With iomeprol neither fatal nor severe reactions were observed. The dye had only little influence on diastolic and systolic blood pressure; heart rate was not significantly influenced. Minor and partly moderate adverse reactions all being completely reversible were observed in 14 patients (18.7%). One patient complained of strong heat sensation after dye injection into the left ventricle. The diagnostic quality of the angiograms allowed to make a definitive diagnosis in all cases. Thus, iomeprol proved to be a suitable and safe contrast medium for heart catheterization.     

Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias

Size and asymmetry (size difference between the left and right sides) of inner ear otoliths of larval cichlid fish were determined after a long-term stay in moderate hypergravity conditions (3g; centrifuge), in the course of which the animals completed their ontogenetic development from hatch to freely swimming. Neither the normal morphogenetic development nor the timely onset and gain of performance of swimming behaviour were impaired by the experimental conditions. However, both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure compared to 1g control specimens raised in parallel. The asymmetry of sagittae was significantly increased in the experimental animals, whereas the respective asymmetry of lapilli was pronouncedly decreased compared with the 1g controls. These findings suggest that growth and development of bilateral asymmetry of otoliths are guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour on transfer to normal 1g earth conditions, which was similar to the behaviour observed in previous experiments on the transfer from 1g to microgravity (parabolic aircraft flights). The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. No differences in asymmetry of sagittae were obtained between the two groups. This supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.     

Comparative hemodynamic effects of amiodarone, sotalol, and d-sotalol

The effects of intravenous boluses of amiodarone (5 mg/kg), racemic sotalol (enantiomeric ratio d/l-sotalol 1:1;1.5 mg/kg), and d-sotalol (0.75 mg/kg) on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), left ventricular end-diastolic pressure (LVEDP), and peak rate of change of left ventricular pressure (LV dp/dt) were assessed in conscious rabbits. Amiodarone and sotalol had a modest negative inotropic effect: amiodarone reduced peak LV dp/dt by 8 +/ 2% (mean +/- SEM) (p < 0.05) and sotalol by 6 +/- 2% (p < 0.05). These two drugs had quite different effects on CO as a result of differences in their actions on peripheral blood vessels: amiodarone caused a 13 +/- 3% (p < 0.05) increase in CO associated with a substantial vasodilatory effect (TPR reduced 25 +/- 3%; p < 0.01); sotalol did not produce any substantial change in either CO or TPR. Bolus intravenous injection of amiodarone was associated with a significant increase in HR (12 +/- 3%; p < 0.01), whereas sotalol reduced HR by 7 +/- 1% (p < 0.05). In contrast, administration of the dextro-rotatory optical isomer, d-sotalol, produced no significant change in peak LV dp/dt, LVEDP, CO, TPR, or HR. These results confirm that amiodarone and racemic sotalol have a comparatively weak cardiodepressant action. The experiments also show that the reduction in cardiac performance associated with racemic sotalol is mediated predominantly through the beta-adrenoreceptor blocking action of the levo-rotatory isomer (l-sotalol) rather than any substantial cardiodepressant effect of the dextro-rotatory isomer.     

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.     

Results of preoperative, peroperative and postoperative hemodynamic recordings in vascular surgery

The alveolar-arterial O2 pressure difference (AaDO2) is composed of three parts which depend on inhomogeneities of the ventilation-perfusion ratio (AaD(distr.) 1), on size and distribution of the diffusing capacity-perfusion ratio (AaD(distr.) 2), and on the effect of the shunt perfusion (AaD(sh)). These three parts can be calculated for normal, hypoxic and hyperoxic breathing conditions if the inhomogeneities of the function parameters and the size of the shunt perfusion are known. The calculation based on experimental data in 28 healthy subjects shows the following results: (1) Under hypoxic breathing conditions the AaD(distr.) 2 due to diffusion dominates. However, even at alveolar O2 pressures below 45 mm Hg the AaD(distr.) 1 must not be ignored. (2) Under normal breathing conditions AaD(distr.) 2 may be ignored and will under pathological conditions become relevant only if the diffusing capacity-perfusion ratio is below 3.10(-3) mm Hg(-1). (3) Under hyperoxic breathing conditions the AaD(sh) is predominant. However, even with the inhalation of pure oxygen, the AaD(distr.) 1 contributes 10% of the total AaDO2. (4) When evaluating the methods of measurement of the O2 diffusing capacity and of the shunt perfusion the inhomogeneities of ventilation, perfusion and diffusion must be considered.     

Gabexate mesilate, a new synthetic serine protease inhibitor: a pilot clinical trial in valvular heart surgery

OBJECTIVE: To assess the effects of gabexate mesilate ([GM], Foy, ONO Pharmaceutical Co, Osaka, Japan) on blood loss in cardiac valve replacement surgery and to establish whether GM reduces blood loss or transfusion requirements after this surgery. DESIGN: Randomized single-blind trial in 30 patients receiving either GM (2 mg/kg/h in a central venous catheter), or no GM, after heparin. SETTING: Department of Anesthesia and Intensive Care, Cardiac Surgery, in a hospital in Italy. PARTICIPANTS: Consent patients. INTERVENTIONS: Cardiac valve replacement surgery. MEASUREMENT AND MAIN RESULTS: Intraoperative and postoperative bleeding, blood transfusion, hemoglobin, and hematocrit were compared. In the GM group bleeding was reduced and no transfusions were required. CONCLUSION: GM appears to play a useful role in reducing blood loss during extracorporeal circulation in cardiac surgery.     

Clinical, endocrine and neurochemical effects of moclobemide in depressed patients

A case of Fraser syndrome diagnosed prenatally is presented. Detection of oligohydramnios, hydrops fetalis and bilateral absence of the kidneys were the initial findings leading to further study. Specific IgM for cytomegalovirus in maternal serum and confirmed infection by fetal blood sampling was an associated finding. The importance of an etiologic diagnosis of nonimmune hydrops and the relevant aspects of genetic counselling are emphasized. The association of the Fraser syndrome with cytomegalovirus infection has not been previously reported.     

Clinical application of a new mobile integrated orbital implant]

Uraemic pancreatopathy is frequently observed in patients with chronic renal failure. The aim of the study was to assess some parameters of exocrine pancreatic function in uraemic patients maintained on intermittent haemodialyses. Elevated serum amylase activity was found in these patients. The most significant finding was the low bicarbonate output in duodenal content after secretin-cerulein stimuli, comparable with that obtained in patients with chronic pancreatitis. It indicates pancreatic exocrine defect in uraemic patients. A fall in protein output and lower amylase activity in duodenal content was also observed in haemodialyzed patients after stimulation. Low basal acid output (BAO) and enhanced maximal (MAO) and peak (PAO) acid outputs were found in uraemic patients after pentagastrin stimulation. Gastritis and duodenitis were frequently diagnosed in endoscopic and histopathological examinations in these patients. In patients with chronic renal failure even without clinical signs of pancreatic, laboratory findings of exocrine pancreatic abnormalities are reported. It may be the cause of uraemic pancreatopathy.     

Short-term hemodynamic effects of mibefradil in dogs with chronic heart failure: comparison with diltiazem

Despite the marked vasodilator and antiischemic actions of existing calcium channel blockers, their use in the treatment of patients with chronic heart failure (HF) remains highly controversial. We compared the short-term hemodynamic effects of i.v. mibefradil, a predominant T-type calcium channel blocker with only partial L-type calcium channel antagonism, and diltiazem, a selective L-type calcium channel antagonist in dogs with chronic HF. Each of three drugs namely, mibefradil, diltiazem and normal saline (as placebo control), were studied in random order (6 days between each drug intervention), in each of 8 dogs with chronic HF produced by multiple intracoronary microembolizations. Intravenous mibefradil and diltiazem were administered as a 100 micrograms/kg bolus followed by a continuous infusion of 6 and 4 micrograms/kg/min, respectively, for 15 min. Equal volumes of normal saline were administered in an identical fashion. In all instances, hemodynamics were obtained at base line and at 5, 10, 15, 30 and 60 min after bolus drug administration. Left ventriculograms were obtained at baseline, and at 15 and 60 min after bolus drug administration. Saline infusion had no effects on hemodynamic or angiographic indexes of left ventricular (LV) function. At 15 min, mibefradil caused significant increases of LV stroke volume and LV ejection fraction compared to baseline (40 +/- 5 vs. 31 +/- 3 ml, P < .05 and 41 +/- 1 vs. 28 +/- 1%, P < .05, respectively). In contrast, at 15 min, diltiazem produced no significant changes of LV stroke volume or ejection fraction compared to baseline despite reducing mean aortic pressure to the same extent as mibefradil. Short-term i.v. mibefradil improves LV function in dogs with chronic HF. The beneficial effects of mibefradil compared to diltiazem may be a consequence of T-type calcium channel selectivity resulting in a vasodilatory response that is free of negative inotropy.     

Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure

This multicenter, open-label study provides the first assessment of the safety and acute hemodynamic effects of a short-term infusion of 15AU81, a chemically stable analog of prostacyclin, in patients with New York Heart Association class III or IV heart failure. Twelve patients underwent sequential dose escalation by increasing the rate of the infusion at 15-minute intervals until the drug was no longer tolerated. Patients then received a 90-minute infusion at their maximum tolerated dose. The infusion was then discontinued and the subjects were observed during a 90-minute washout segment. Serial hemodynamic measurements were made throughout the dose-ranging, maintenance, and washout segments. A significant decrease in systemic vascular resistance (1,935 +/- 774 vs 1,243 +/- 351 dynes.s.cm-5; p < 0.001) and pulmonary vascular resistance (395 +/- 335 vs 223 +/- 198 dynes.s.cm-5; p = 0.008) occurred from the infusion of vehicle to the maximum tolerated dose. During dose titration, there was a a significant increase in cardiac index (1.9 +/- 0.7 vs 2.6 +/- 0.6 liters/min/m2; p < 0.001) and a tendency for a mild reduction in pulmonary artery wedge pressure (18 +/- 7 vs 17 +/- 6; p = 0.055) for the 8 patients with values on vehicle and maximum tolerated dose. These hemodynamic changes persisted during the maintenance infusion and disappeared rapidly during the washout segment. The most common adverse event to limit dose-ranging was headache, which occurred at a mean maximum tolerated dose of 36 +/- 15 ng/kg/min. Administration of 15AU81 was associated with significant acute hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of SIV infection in rhesus monkeys

A model is proposed in which a neurovirulent, microglial-passaged, simian immunodeficiency virus (SIV) is used to produce central nervous system (CNS) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (HIV). The time course of disease progression was characterized by using functional measures of cognition and motor skill, as well as neurophysiologic monitoring. Concomitant assessment of immunological and virological parameters illustrated correspondence between impaired behavioral performance and viral pathogenesis. Convergent results were obtained from neuropathological findings indicative of significant CNS disease. In ongoing studies, this SIV model is being used to explore the behavioral sequelae of immunodeficiency virus infection, the viral and host factors leading to neurologic dysfunction, and to begin testing potential therapeutic agents.     

Time-dependent hemodynamic effects of monosan (Isosorbide-5-mononitrate) in anginal patients

Clinical efficacy of 3rd generation cephalosporins i.e. oral cefpodoxime and parenteral ceftriaxone was studied in the treatment of children with oncohematologic pathology. Cefpodoxime proved to be efficient in cases of moderate infectious complications in regard to the respiratory tracts. The oral administration of the drug provided its usage in outpatients. Ceftriaxone had a favourable effect in the treatment of children with more severe processes as a rule at the background of agranulocytosis and a lower immune response often with a tendency to generalization. No side effects of the cephalosporins were observed.