Sustained pulmonary vasodilation after inhaled nitric oxide for hypoxic pulmonary hypertension in swine

It has been shown that pulmonary vasodilation is sustained after discontinuation of inhaled nitric oxide (INO) during moderate hypoxic pulmonary hypertension (HPH) in swine. The present investigations demonstrated how INO dose, hypoxia duration, and endogenous NO production influence this important phenomenon. Fifteen adolescent Yorkshire swine were randomly assigned to three groups (n = 5 each) and underwent the following phasic experimental protocol: (I) Baseline ventilation (FIO2 = .3); (II) Initiating HPH (FIO2 = .16 to .18, PaO2 = 45 to 55 mm Hg); (III) INO at 10 ppm; (IV) Posttreatment observation; (V) INO of 80 ppm; and (VI) Posttreatment observation. Phase II (pretreatment hypoxia) lasted 30 minutes in group A (short hypoxia) and 120 minutes in group B (long hypoxia). N-nitro-L-arginine methyl ester (NAME) was used to inhibit nitric oxide synthase (NOS) throughout the experiment in group C (short hypoxia + NAME). Hemodynamics and blood gases were monitored by systemic and pulmonary artery catheters placed by femoral cutdown. Analysis of variance with post-hoc adjustment was used to compare groups at each phase, and the paired t test was used for comparisons within a group. With respect to baseline mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR), there were no significant differences among the three groups. MPAP and PVR were significantly higher in group C than in group A during phase II, (MPAP, 76% +/- 8% v 33% +/- 2%; PVR, 197% +/- 19% v 78% +/- 10%; P < .05). There were no significant differences in MPAP or PVR during phases III through VI. When MPAP was expressed as percent dilation, 80 ppm caused significantly more dilation than did 10 ppm in all three groups. Groups A and C had significantly higher sustained pulmonary artery dilation after 80 ppm than after 10 ppm (A, 82% +/- 31% v 17% +/- 11%; C, 68% +/- 10% v 42% +/- 12%; both P < .05), but group B did not (43% +/- 15% v 30% +/- 9%; P = .25). High dose results in stronger vasodilation than low dose during and after INO for moderate HPH of short duration. Long hypoxia blunts this high-dose advantage. Endogenous NO inhibition augments HPH but does not decrease pulmonary vasodilation during or after INO.     

Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension

Using a prospective audit, we have evaluated the efficacy of an integrated autotransfusion regimen which comprised predepositing and intra- and postoperative blood salvage in major orthopaedic surgery. We examined prospectively the records of 1785 patients (1198 females, 5867 males, mean age 62 (range 16-90) yr, preoperative haemoglobin concentration 13.4 (SD 1.4) g dl-1) undergoing total hip arthroplasty (THA, 1229 patients), THA after removal of internal fixation devices (RFD + THA, 18 patients), total knee arthroplasty (TKA, 263 patients), revision surgery of the hip (HR cup + stem revision, 197 patients; cup revision, 53 patients; stem revision, 16 patients) and total knee revision (TKR, nine patients). We estimated that the number of predonations (MSBOS = maximum surgery blood order schedule) was 2 u. for THA, TKA and TKR, and 3 u. for partial or total hip revision and total hip arthroplasty with fixation removal. We found that it was possible to obtain the MSBOS in 1597 patients (89.5%). Homologous red blood cell (HRBC) transfusions were carried out in 131 patients (7.3%). We found that the need to use HRBC was significantly associated with failure to meet the number of MSBOS, female sex, lower preoperative haemoglobin concentration, use of calcium heparin for antithrombosis prophylaxis, more extensive surgery, higher ASA rating and co-existing diseases such as coronary artery disease.     

Treatment of pulmonary hypertension with inhaled nitric oxide during hepatic transplantation in an adolescent: reversibility of pulmonary hypertension after transplantation

Accusations of rape or sexual harassment are currently very high-profile in the military. This article discusses rape allegations in the military legal system from a psychiatric perspective. The original definition of "rape trauma syndrome" and subsequent psychiatric thinking about the diagnosis are briefly outlined. Common reactions seen in military victims in this era are described. A prototypical military case is presented. An adequate evaluation of an alleged victim is outlined. Credentials and preparation of an expert witness are also briefly discussed, with cautions about the use of expert testimony in cases of alleged sexual assault and rape trauma syndrome.     

Single- versus double-lung transplantation for pulmonary hypertension

OBJECTIVES: Uncertainty persists as to the best lung transplant operation for patients with pulmonary hypertension. To quantify short- and long-term outcomes after single- and double-lung transplantation for pulmonary hypertension, we reviewed our clinical experience. METHODS: A retrospective review of 58 lung transplants at a single institution between 1989 and 1996 was performed. Recipients had primary (n = 19) or secondary (n = 39) pulmonary hypertension. RESULTS: Thirty-seven double- and 21 single-lung transplants were performed. The groups were well matched with regard to preoperative characteristics. Cardiopulmonary bypass time was longer (151 vs 250 minutes) in the double-lung group. Excluding 10 patients surviving less than 30 days (6 double- and 4 single-lung transplants), median duration of intubation (7.5 vs 10 days), length of stay in the intensive care unit (10 vs 16 days), and hospital stay (32 vs 52 days) were not significantly different for the single- and double-lung groups, respectively. Actuarial survival was nearly identical, with 81% and 84% 1-month survivals for the single- and double-lung groups, and identical 1-year (67%) and 4-year (57%) survivals for both groups. Late functional status was similar for recipients of single- and double-lung grafts. During the period of this study, 58 patients with pulmonary hypertension died on our center's waiting list before coming to transplantation. CONCLUSIONS: These data suggest that lung transplant recipients with pulmonary hypertension have similar outcomes after single- or double-lung transplantation. These results support cautious preferential application of single-lung transplantation for pulmonary hypertension.     

Clinical response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn

We observed clinical response to inhaled nitric oxide (iNO) in 12 neonates with persistent pulmonary hypertension of the newborn (PPHN). Clinical response was defined as a decrease in oxygenation index (OI) by 40%. Ten of 12 neonates had response to iNO showing decrease OI from 46.1+/-7.6 to 14.4+/-6.8 at 1 hour after inhalation. Sustained improvement of OI was achieved in 8 neonates and two neonates were relapsed. In the group of neonates who had OI above 40 (n=7), 6 of them showed the decrease of OI from 66.1+/-4.8 to 18.3+/-8.0 at 1 hour. In two groups, one had OI of 40 or greater, and the other OI of 40 or less, there were no differences in pattern of response and early death rate. The response rates according to underlying diseases were as follows; idiopathic PPHN 100%, respiratory distress syndrome 100%, and diaphragmatic hernia 66.7%. Relapse was observed in one neonate with sepsis caused by pneumonia and in one infant with meconium aspiration syndrome. Two infants showed no response to iNO (one diaphragmatic hernia and one suspected pulmonary hypoplasia). We conclude that iNO therapy could improve oxygenation in high percentage of newborn infants with severe PPHN of various underlying conditions except pulmonary hypoplasia.     

Effects of inhaled nitric oxide and oxygen in high-altitude pulmonary edema

BACKGROUND: High-altitude pulmonary edema (HAPE) is characterized by pulmonary hypertension, increased pulmonary capillary permeability, and hypoxemia. Treatment is limited to descent to lower altitude and administration of oxygen. METHODS AND RESULTS: We studied the acute effects of inhaled nitric oxide (NO), 50% oxygen, and a mixture of NO plus 50% oxygen on hemodynamics and gas exchange in 14 patients with HAPE. Each gas mixture was given in random order for 30 minutes followed by 30 minutes washout with room air. All patients had severe HAPE as judged by Lake Louise score (6.4+/-0.7), PaO2 (35+/-3. 1 mm Hg), and alveolar to arterial oxygen tension difference (AaDO2) (26+/-3 mm Hg). NO had a selective effect on the pulmonary vasculature and did not alter systemic hemodynamics. Compared with room air, pulmonary vascular resistance fell 36% with NO (P<0.001), 23% with oxygen (P<0.001 versus air, P<0.05 versus NO alone), and 54% with NO plus 50% oxygen (P<0.001 versus air, P<0.005 versus oxygen and versus NO). NO alone improved PaO2 (+14%) and AaDO2 (-31%). Compared with 50% oxygen alone, NO plus 50% oxygen had a greater effect on AaDO2 (-18%) and PaO2 (+21%). CONCLUSIONS: Inhaled NO may have a therapeutic role in the management of HAPE. The combined use of inhaled NO and oxygen has additive effects on pulmonary hemodynamics and even greater effects on gas exchange. These findings indicate that oxygen and NO may act on separate but interactive mechanisms in the pulmonary vasculature.     

Effectiveness of continuous intravenous prostaglandin E 1 against pulmonary hypertension]

Teratogenicity studies of methyl bromide, a widely used fumigant, were conducted in rats and rabbits. Methyl bromide was dissolved in corn oil and administered orally to groups of 24 copulated female Crj:CD (SD) rats at dose levels of 0 (corn oil), 3, 10 or 30 mg/kg/day on days 6-15 of gestation and to groups of 18 artificially inseminated female Kbl:JW rabbits at 0, 1, 3 or 10 mg/kg/day on days 6-18 of gestation. Maternal rats and rabbits were euthanized on respective days 20 and 27 of gestation. Foetuses were examined for survival, growth and teratological alterations. Maternal toxicity was evident in the high-dose groups for both species. In these groups, maternal body weight gains and food consumption were significantly decreased during the dosing and post-dosing periods. Necropsy of maternal rats also revealed erosive lesions in the stomach and the surrounding organs. However, no treatment-related adverse effects were found in foetuses of the treated groups for both rat and rabbit studies. These results led to the conclusion that methyl bromide was not foetotoxic or teratogenic to rat and rabbit foetuses up to dose levels of 30 and 10 mg/kg/day, respectively, at which maternal toxicity was evident for both species.     

In pigs, inhaled nitric oxide (NO) counterbalances PAF-induced pulmonary hypertension

In 6 anesthetized mechanically ventilated pigs we have studied the effects of inhalation of 80 ppm of nitric oxide (NO) before and after platelet-activating factor (PAF) administration (50 ng/kg iv). Our results show that NO inhalation causes a decrease in pulmonary arterial pressure and in heart rate without affecting other circulatory parameters. PAF administration causes a pulmonary hypertension and a prompt and brief decrease in systemic pressure. Inhalation of NO reduces the pulmonary hypertension, without completely reversing PAF-dependent vasoconstriction. PAF administration to pigs pretreated with indomethacin produces a lesser increase in pulmonary vascular pressure. In this case, NO inhalation can restore to baseline values. Pretreatment of 3 of the 6 pigs with NG-nitro-L-arginine-methyl-ester did not prevent the prompt and brief PAF-induced systemic hypotension. In conclusion, our results show that NO reduces basal pulmonary vascular tone, acts as a pulmonary vasodilator on PAF-preconstricted vessels and is not involved in the brief systemic hypotension consequent to PAF administration.     

Right ventricular size is acutely decreased by inhaled nitric oxide in newborns with pulmonary hypertension

The pressure and volume demands of the right and left ventricles may dramatically change following selective pulmonary vasodilation in newborns with pulmonary hypertension. Thus, ventricular planimetry was performed by two-dimensional echocardiography in 35 newborns with lung disease and increased pulmonary vascular resistance who were treated with inhaled nitric oxide to determine the influence of therapy on right and left ventricular size and function. The end-diastolic and end-systolic areas of each ventricle were measured from apical 4-chamber images before, and 30 to 60 minutes after, the onset of 20 parts per million inhaled nitric oxide. Estimates of ventricular function were determined by the systolic decrease in ventricular area, (diastolic area - systolic area) x 100/diastolic area. Heart rate, systemic blood pressure, and left ventricular areas did not change. However, the oxygenation index, the proportion of right-to-left ductal shunt (nonrestrictive ductus arteriosus, n = 22), the systolic pulmonary arterial pressure (closed or restrictive ductus arteriosus, n = 13), and the right ventricular diastolic and systolic areas were decreased after nitric oxide inhalation. The baseline systolic decrease in left ventricular area was lower in a subgroup of patients who developed an increase in left ventricular diastolic area following nitric oxide inhalation. Thus, nitric oxide improves pulmonary hemodynamics and decreases right ventricular size in newborns with lung disease and pulmonary hypertension. However, newborns may develop an increase in left ventricular size if left ventricular function is decreased prior to therapy.     

Dipyridamole attenuates rebound pulmonary hypertension after inhaled nitric oxide withdrawal in postoperative congenital heart disease

While much is known about the functional significance of strategic decisions in animal fighting, relatively little is understood about the mechanisms that underlie the making of those decisions. In mechanistic terms, strategic decisions, such as either escalating a fight or giving up, are made in relation to the proximate costs that opponents inflict (or can potentially inflict) upon one another. These costs include physical injury and also the physiological consequences of engaging in an energetically demanding activity. We studied the role of injury and energy metabolism during fights between male cichlid fish, Tilapia zillii. In relation to injuries incurred during fights, scale loss differed depending on whether the winner was smaller or larger than its opponent; smaller winners inflicted significantly more damage on their opponents than they received, whereas this difference was not apparent in those fights won by the larger fish. In relation to energy metabolism, escalated fighting resulted in a significant depletion of total sugar reserves in the muscle and the liver. It appears that the muscle energy reserves are respired anaerobically, as was evident from the accumulation of lactate in the muscle. Losers had significantly higher levels of muscle lactate than winners. Together, the injury data and the metabolic data suggest that escalated fighting is costly for both winners and losers, but especially so for losers. These data are discussed in relation to models of animal decision making and we conclude that the difference between opponents in the proximate costs incurred during fighting is likely to underlie the making of decisions such as continuing, giving up or escalating the fight. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in experimental pulmonary hypertension

BACKGROUND: The role of endogenous nitric oxide (NO) in the regulation of pulmonary vascular tone is complex. Inhibition of endogenous NO synthase, potentially through upregulation of guanylyl cyclase, results in an increase in potency of nitrovasodilators in the systemic circulation. This study considered whether inhibition of endogenous NO synthase would increase the potency of nitrovasodilators, but not of cyclic adenosine monophosphate-dependent vasodilators, in the pulmonary vasculature. METHODS: We used the isolated buffer-perfused rabbit lung. Preparations were randomized to receive either pretreatment with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO synthase) or no pretreatment. Stable pulmonary hypertension was then produced by infusing the thromboxane A2 analog U46619. The dose-response characteristics of two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were studied. RESULTS: Inhibition of endogenous NO synthase caused no significant changes in baseline pulmonary artery pressure but did significantly reduce the U46619 infusion rate required to produce pulmonary hypertension. Pretreatment with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log median effective dose with sodium nitroprusside and nitroglycerin. In contrast, pretreatment with L-NAME resulted in no changes in the dose-response characteristics of the cyclic adenosine monophosphate-mediated, NO-independent vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine. CONCLUSIONS: These data suggest that endogenous NO synthase is not an important regulator of basal pulmonary tone in this model but is an important modulator of pulmonary vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may depend on the level of activity of NO synthase.     

Effects of ginkgolide B on isobaric hypoxic pulmonary hypertension in rats

We examined the effects of ginkgolide B (BN52021), a specific platelet activating factor (PAF) antagonist, on hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Chronic hypoxia can cause pulmonary hypertension and pulmonary vascular remodeling in rats. Treated with BN52021, the rat's pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy at 3 weeks of hypoxic exposure (FiO2 = 0,10) could be reduced. The results suggest that PAF contributes to the development of chronic hypoxic pulmonary hypertension and pulmonary vascular remodeling, and PAF antagonist may be an useful agent for preventing hypoxic pulmonary hypertension.     

Effects of intravenous medium-chain triglycerides on pulmonary gas exchanges in mechanically ventilated patients

OBJECTIVE: In mechanically ventilated patients, pulmonary gas exchange was investigated during the administration of total parenteral nutrition containing medium-chain triglycerides or long-chain triglycerides as fat emulsions. DESIGN: Prospective, randomized, crossover trial (two lipid infusion periods of 8 hrs). SETTING: Intensive care unit in a university hospital. PATIENTS: Six mechanically ventilated patients, using the pressure-support mode. INTERVENTIONS: Total caloric intake was adapted according to measured energy expenditure. Fat emulsion provided 50% of the energy expenditure. Patients were infused with 50% medium-chain/50% long-chain triglycerides or 100% long-chain triglycerides in a random sequence. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption, CO2 production, and minute ventilation were measured by indirect calorimetry. PaO2 and PaCO2 were determined in blood samples. Medium-chain triglycerides increased oxygen consumption by 27.8% and minute ventilation by 14.3% at the end of the protocol. CO2 production, PaO2, and PaCO2 were not different between groups. CONCLUSIONS: Medium-chain triglycerides cause an increase in metabolic demand in mechanically ventilated patients when they are infused over a short period. Postoperative or intensive care unit patients with a low pulmonary reserve should receive infusions of medium-chain triglycerides over a more prolonged period than long-chain triglycerides.     

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide

The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises.     

Continuous therapy with intravenous prostacyclin for primary pulmonary hypertension: a bridge to heart-lung transplantation

Primary pulmonary hypertension (PPH) continues to be a major problem. Vasodilator therapy has been of variable success in selected patients. Recently, with the introduction of prostacyclin (Prostaglandin I2, epoprostenon) as a potent vasodilator, several reports have shown a positive effect in primary pulmonary hypertension. We report here two patients with PPH who responded favorably to continuous intravenous therapy with prostacyclin. Both patients responded with a reduction in pulmonary vascular resistance, increase in cardiac output and dramatic improvement of right heart failure. Although therapy with prostacyclin is extremely expensive it may be used as a bridge to heart-lung transplantation in patients with end-stage PPH who do not respond adequately to alternative therapy.     

Partitioning of pulmonary vascular resistance in primary pulmonary hypertension

OBJECTIVES: This study sought to determine the site of increased pulmonary vascular resistance (PVR) in primary pulmonary hypertension by standard bedside hemodynamic evaluation. BACKGROUND: The measurement of pulmonary vascular pressures at several levels of flow (Q) allows the discrimination between active and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and may detect the presence of an increased pulmonary vascular closing pressure. The determination of a capillary pressure (Pc') from the analysis of a Ppa decay curve after balloon occlusion allows the partitioning of PVR in an arterial and a (capillary + venous) segment. These approaches have not been reported in primary pulmonary hypertension. METHODS: Ppa and Pc' were measured at baseline and after an increase in Q induced either by exercise or by an infusion of dobutamine, at a dosage up to 8 microg/kg body weight per min, in 11 patients with primary pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of prostacyclin. RESULTS: At baseline, Ppa was 52+/-3 mm Hg (mean value+/-SE), Q 2.2+/-0.2 liters/min per m2, and Pc' 29+/-3 mm Hg. Dobutamine did not affect Pc' and allowed the calculation of an averaged extrapolated pressure intercept of Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc' and PVR. Exercise increased Pc' to 40+/-3 mm Hg but did not affect PVR. CONCLUSIONS:ns. These findings are compatible with a major increase of resistance and reactivity at the periphery of the pulmonary arterial tree.     

The influence of continuous intravenous prostacyclin therapy for primary pulmonary hypertension on the timing and outcome of transplantation

BACKGROUND: Primary pulmonary hypertension (PPH) is a progressive disease with a median survival of less than 3 years from diagnosis. Medical management has typically consisted of anticoagulation and oral calcium channel blocking agents, whereas lung transplantation (LT) has been reserved for patients who are unresponsive to medical therapy. Continuous intravenous prostacyclin was introduced for patients who did not respond to calcium channel blockers and who would have required LT. We reviewed our experience with prostacyclin in LT candidates to study its effects on the timing and outcome of LT. METHODS: We retrospectively reviewed the clinic and hospital records of patients with PPH who were both treated with prostacyclin and evaluated for LT. Additional information was obtained from the pulmonary vascular disease and lung transplantation databases. RESULTS: A total of 42 patients were identified who received prostacyclin for the treatment of PPH and were evaluated for LT. Thirty-seven patients were accepted as LT candidates, 22 at The University of Maryland Medical Center (UMMC), 15 at other LT programs. Overall, 70% (27/37) of LT candidates were removed from the LT waiting list or had listing for LT deferred because of clinical improvement. In patients listed for LT before initiation of prostacyclin therapy, 55% (12/22) were removed from the active waiting list for 27.2+/-17 months (range 8 to 60), and 92% (11/12) remain on the inactive status. In patients who received prostacyclin before listing for LT, listing for LT was deferred in 94% (14/15) for 17.4+/-9 months (range 6 to 33 months) because of clinical stability or improvement. In all, 93% of patients (39/42) experienced an improvement in 1 or more New York Heart Association functional class. The hemodynamic profiles of the eight patients removed from the active waiting list at UMMC demonstrated increases of 55%+/-18% in cardiac output, and decreases of 14.3%+/-4.9% in mean pulmonary artery pressure and 36%+/-8.3% in total pulmonary resistance (p < 0.05). The 1-year survival rate for LT after prostacyclin therapy was 88% (7/8) at UMMC and 60% (3/5) at the other centers. CONCLUSION: We conclude that prostacyclin therapy is an effective means of delaying, possibly indefinitely, the need for LT in patients with PPH and that excellent results can be obtained when LT is performed after prostacyclin therapy. Consideration should be given to initiating prostacyclin therapy in all patients whose conditions do not respond to conventional therapy before proceeding with transplantation.     

Effect of intravenous verapamil in experimental ventricular arrhythmia

Experimental ventricular tachycardias (VT) were provoked in dog hearts with minute crystals of aconitine introduced into the periphery of an infarcted area, produced by intramural injection of 1-1.5 ml of phenol. The response of these tachycardias to verapamil was studied. Leads II, aVL, intraventricular right and left unipolar records, as well as one on the superior vena cava were registered under control conditions, with VT and after the injection of the antiarrhythmic agent. This injection was infused into superior vena cava over 15-20 minutes. Records were obtained with constant intervals, waiting for the recovery of sinus rhythm (SR) and the posterior reappearance of ventricular tachycardia. The experiments were performed 6 to 8 hs with continuous infusion of Hartmann's solutions. Throughout these periods, the variations of systemic systolic pressure were registered. Of the 75 dogs treated with 0.2 mg/kg of verapamil, SR was recovered transiently in 30 (40%), while it exerted no antiarrhytmic effect in 19 (25%). Arterial systolic pressure fell importantly in 10 animals (13%). In 3 other groups, of 15 dogs each, comparative administration of verapamil vs lidocaine (I), vs mexiletine (II) and vs propafenone (III), was tried. In Group I, verapamil reestablished transient SR in 73% and lidocaine in only 7%; in II, SR resulted from verapamil in 33% and from mexiletine in 7%; in III, SR reappeared in 21% with verapamil and in 28% with propafenone. The repeated positive effect of verapamil was found in 33% of 15 experiments. This drug is effective in certain experimental ventricular tachycardias, probably related to calcium-dependent potentials.