Asymmetry of retrograde conduction and reentry within the His-Purkinje system: a comparative analysis of left and right ventricular stimulation.

OBJECTIVES: The purpose of this study was to delineate retrograde His-Purkinje system conduction and reentry (V3 phenomenon) during left ventricular extrastimulation and compare them with right ventricular extrastimulation. BACKGROUND: The V3 phenomenon has been well described in the past during right ventricular extrastimulation; however, it has not been studied systematically during left ventricular extrastimulation. METHODS: Left and right ventricular pacing were performed in 13 patients. Retrograde and anterograde routes of impulse propagation were determined on the basis of the sequence of His (H) and right bundle (RB) potentials, H-RB intervals, as well as the QRS configuration and axis of V3 beats. RESULTS: During right ventricular pacing, retrograde conduction of V2, when discernible, occurred exclusively through the left bundle at all coupling intervals equal to or shorter than the His-Purkinje relative refractory period, with the exception of two isolated beats. During left ventricular extrastimulation, His bundle activation was through the left bundle in nine patients and through the right or left bundle in three other patients. In one patient, the route could not be determined. The V3 phenomena occurred in eight patients during right ventricular pacing. Seven patients had a left bundle branch block pattern QRS configuration, and one had a right bundle branch block pattern configuration. V3 beats occurred in five patients during left ventricular apex pacing: left bundle branch block pattern configuration in one patient and right bundle branch block pattern configuration in four. In three of these four patients, the reentry was interfascicular and limited to the left bundle branch system. CONCLUSIONS: The left-sided His-Purkinje system is the preferred retrograde route of impulse propagation during both left and right ventricular extrastimulation. Reentry within the His-Purkinje system elicited by right ventricular extrastimulation involves both bundle branches, whereas this reentry tends to occur within the left-sided His-Purkinje system during left ventricular pacing.

Comparison of the hemodynamic effects of nitric oxide and endothelium-dependent vasodilators in intact lungs.

The effects of endothelium-dependent vasodilation on pulmonary vascular hemodynamics were evaluated in a variety of in vivo and in vitro models to determine 1) the comparability of the hemodynamic effects of acetylcholine (ACh), bradykinin (BK), nitric oxide (NO), and 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP), 2) whether methylene blue is a useful inhibitor of endothelium-dependent relaxing factor (EDRF) activity in vivo, and 3) the effect of monocrotaline-induced pulmonary hypertension on the responsiveness of the pulmonary vasculature to ACh. In isolated rat lungs, which were preconstricted with hypoxia, ACh, BK, NO, and 8-bromo-cGMP caused pulmonary vasodilation, which was not inhibited by maximum tolerable doses of methylene blue. Methylene blue did not inhibit EDRF activity in any model, despite causing increased pulmonary vascular tone and responsiveness to various constrictor agents. There were significant differences in the hemodynamic characteristics of ACh, BK, and NO. In the isolated lung, BK and NO caused transient decreases of hypoxic vasoconstriction, whereas ACh caused more prolonged vasodilation. Pretreatment of these lungs with NO did not significantly inhibit ACh-induced vasodilation but caused BK to produce vasoconstriction. Tachyphylaxis, which was agonist specific, developed with repeated administration of ACh or BK but not NO. Tachyphylaxis probably resulted from inhibition of the endothelium-dependent vasodilation pathway proximal to NO synthesis, because it could be overcome by exogenous NO. Pretreatment with 8-bromo-cGMP decreased hypoxic pulmonary vasoconstriction and, even when the hypoxic pressor response had largely recovered, subsequent doses of ACh and NO failed to cause vasodilation, although BK produced vasoconstriction. These findings are compatible with the existence of feedback inhibition of the endothelium-dependent relaxation by elevation of cGMP levels. Responsiveness to ACh was retained in lungs with severe monocrotaline-induced pulmonary hypertension. Many of these findings would not have been predicted based on in vitro studies and illustrate the importance for expanding studies of EDRF to in vivo and ex vivo models.

Effects of non-REM sleep upon respiratory drive and the respiratory pump in humans.

We observed that ventilation fell and end-tidal CO2 rose in the change from wakefulness to non-REM (NREM) sleep in 4 normal human subjects studied on two nights each. We hypothesized that the observed ventilatory depression was due to effects of sleep both upon the central respiratory neural output and upon the mechanical respiratory pump. Both the central controller response to CO2, as measured by diaphragmatic and intercostal EMG activity, and the ability of the respiratory pump in effecting ventilation in response to diaphragmatic or intercostal activation, as measured by the relationship between the EMG activities and minute ventilation, are reduced in NREM sleep. We describe a general method of apportioning the separate effects of sleep, or other factors, upon the central respiratory controller, the respiratory mechanical pump, and the metabolic rate, in determining the total observed increase in end-tidal CO2.

Long-term clinical outcome of right bundle branch radiofrequency catheter ablation for treatment of bundle branch reentrant ventricular tachycardia.

The study assessed the long-term outcome of patients undergoing radiofrequency ablation of the right bundle for bundle branch reentrant ventricular tachycardia. Bundle branch reentrant tachycardia was diagnosed in 16 patients (ejection fraction 31% +/- 15%) who underwent electrophysiology study in our laboratory. All patients had His-Purkinje system conduction delay with mean HV interval of 68 +/- 8 ms. After ablation, right bundle branch block developed in 15 patients. One patient developed complete heart block, which was anticipated. One patient died of heart failure 9 months after ablation. Two patients were successfully bridged to heart transplantation 0.5 and 13 months, respectively, after ablation. Two patients received implantable defibrillators for other ventricular tachycardias. One patient had syncope 11 months after ablation, but there was no evidence of ventricular tachycardia or heart block in repeat electrophysiology study. This patient died suddenly 29 months after ablation. The remaining nine patients were alive and well for a mean follow-up of 19 +/- 10 months. Radiofrequency ablation of the right bundle branch is an effective therapy for treatment of bundle branch reentrant ventricular tachycardia. Survival is excellent provided that other types of ventricular tachycardia, when present, are treated as well. This technique may be helpful in management of patients who have unacceptable frequent shocks from their implanted defibrillators and may be helpful in avoiding implantation of such a device completely in others. In some patients with terminal heart failure and incessant ventricular tachycardia, this procedure can function as a bridge to cardiac transplantation.

Dynamic changes of hypoglossal and phrenic activities by hypoxia and hypercapnia.

Steady-state responses of unanesthetized subjects to hypercapnia or hypoxia provide no evidence that chemoreceptor afferents are differentially distributed upon hypoglossal and bulbospinalphrenic neurons, as suggested by results in anesthetized animals. We hypothesized that dynamic changes in activities of phrenic and hypoglossal nerves might differ following sudden alterations of inspired gases. This hypothesis was based on the observation that episodes of obstructive apnea may follow central apnea. The obstruction might reflect phrenic activity increasing more quickly than that of the hypoglossal upon resumption of ventilation. In decerebrate, vagotomized, paralyzed and ventilated cats, we recorded phrenic and hypoglossal activities before and during abrupt, sustained exposure to hypercapnia, hypoxia and hypoxic hypercapnia, and following sudden withdrawal of these stimuli. For all such manoeuvres, activities of phrenic and hypoglossal nerves increased or decreased in parallel fashion. Our findings cause rejection of the hypothesis of differing dynamic phrenic and hypoglossal responses to chemoreceptor stimuli. The concept that the ventilatory control system is well organized to prevent upper airway obstructions is discussed.

Smaller capacitors improve the biphasic waveform.

INTRODUCTION: Current implantable cardioverter defibrillators (ICDs) use relatively large capacitance values. Theoretical considerations suggest, however, that improved defibrillation energy requirements may be obtained with smaller capacitance values. METHODS AND RESULTS: We compared the energy requirement for defibrillation in a porcine model using a biphasic waveform generated from two capacitance values of 140 microF and 85 microF. Phase 1 reversal of the shock waveform occurred at 65% tilt. Phase 2 pulse width was equal to phase 1. Shocks were delivered through epicardial patch electrodes after 10 seconds of induced ventricular fibrillation. The defibrillation threshold (DFT) was determined by a "down-up" technique requiring three reversals of defibrillation success or failure. The DFT was defined as the average of the values obtained with all trials starting from the successful shock prior to the first failure to defibrillate to the last successful defibrillation. In eight experiments, the measured parameters at DFT were as follows. The average stored and delivered DFT energies for the 85 microF capacitor were 6.1 +/- 2.1 and 6.0 +/- 2.0 J, respectively, compared to 7.5 +/- 1.3 and 7.4 +/- 1.3 J for the 140 microF capacitor (P < 0.04). The phase 1 pulse widths were significantly shorter for the 85 microF capacitor (5.1 +/- 0.8 msec vs 9.2 +/- 1.3 msec) and the impedances were lower (54.4 +/- 5.8 omega vs 59.9 +/- 6.3 omega). The mean leading edge voltage was trending higher for the 85 microF capacitor, but this difference did not reach statistical significance (374 +/- 63 V vs 326 +/- 30 V; P = 0.055). CONCLUSION: Smaller capacitance values do result in lower energy requirements for the biphasic waveform, at a possibly higher leading edge voltage and a much shorter pulse width. Smaller capacitance values could represent a significant enhancement of well-established benefits demonstrated with the biphasic waveform.

Long-term survival and complications in patients with malignant ventricular tachyarrhythmias: treatment with a nonthoracotomy implantable cardioverter defibrillator with or without a subcutaneous patch.

The Endotak lead system and ICD has been used to treat patients with malignant ventricular arrhythmias. We analyzed the clinical characteristics of 1,053 patients who underwent implantation of the Endotak lead system with or without a subcutaneous patch. Group A consisted of 567 patients receiving the Endotak lead with a subcutaneous patch; group B consisted of 486 patients receiving the Endotak lead alone. The 2-year survivals from sudden death, cardiac death, and total death in groups A and B were 97.6%/98.2% (P = 0.38), 88.6%/92.7% (P = 0.09), and 84.7%/86.8% (P = 0.06), respectively. Minimum tested effective defibrillation energy at implantation was 17.2 +/- 5.2 J for group A and 15.8 +/- 5.1 J for group B (P < 0.01). The operative mortality was 1.8% in group A and 0.6% in group B (P = 0.09). The incidence of lead dislodgment, malfunction, and infection was 6.7% for group A and 3.5% for group B (P < 0.01). Sudden death survival was excellent in both groups with less lead complications in group B. The Endotak lead alone may be the preferred choice of lead configuration in those patients who have adequate defibrillation thresholds at implant.

Human neurophysins in carcinoma of the lung: relation to histology, disease stage, response rate, survival, and syndrome of inappropriate antidiuretic hormone secretion.

At diagnosis, 65% of 103 patients with small cell carcinoma of the lung were found to have elevated plasma concentrations of vasopressin-associated human neurophysin (VP-HNP), oxytocin-associated human neurophysin (OT-HNP), or both, which were thought to be related to tumor secretion of these proteins. The remainder of patients were designated as nonsecretors (24%) or possible secretors (11%), depending upon plasma concentration of the neurophysins prior to therapy. There was a significantly higher percentage of secretors among patients with extensive disease (82%) than among those with limited disease (40%) (P = 0.001). However, within each stage group, there was no correlation between secretory status and response to therapy, survival, or histologic subtype. In addition, patients who initially were nonsecretors or possible secretors maintained this status throughout the course of disease remission and subsequent relapse. These findings suggest the possibility of biochemical differences between tumors which present as limited disease and those which present as extensive disease. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was infrequent in limited disease but was present in 33% of patients with extensive disease. SIADH was not seen without VP-HNP elevation; however, with extensive disease, 49% of patients with elevated VP-HNP had SIADH. In contrast, elevated plasma concentrations of the neurophysins were seen in only 19.6% of 56 patients with non-small cell carcinoma of the lung. The levels were in general lower than those in patients with small cell carcinoma and were seen at approximately equal frequencies in each major cellular subtype.