Usefulness of the bidirectional Glenn procedure as staged reconstruction for the functional single ventricle.

The bidirectional Glenn operation may be particularly useful as an intermediate procedure before Fontan correction in high-risk patients. From October 1989 through February 1992, 50 patients 1 to 60 months old (median 12) have undergone a bidirectional Glenn operation. Diagnoses included hypoplastic left heart syndrome in 21 patients, pulmonary atresia with intact ventricular septum in 10, tricuspid valve atresia in 9, other complex univentricular heart defects in 9, and Ebstein's anomaly in 1. Mean pulmonary vascular resistance was 2.2 +/- 0.2 Wood U (range 0.5 to 7.3) and mean pulmonary artery area Nakata index was 318 +/- mm2/m2 (range 80 to 821). Additional procedures were performed in 17 patients, including pulmonary artery reconstruction in 15 (29%) and bilateral caval anastomoses in 5 (10%). There were 4 hospital deaths (8%). Two deaths resulted from myocardial infarction in patients with pulmonary atresia with intact ventricular septum and sinusoids and 1 from severe pulmonary vascular disease in a patient with hypoplastic left heart syndrome. There was 1 late death from pneumonia. Actuarial survival is 92 +/- 4% at 1 month and beyond, with a mean follow-up of 13.4 +/- 1 months. Risk factor analysis showed that pulmonary vascular resistance > 3 Wood U and pulmonary artery distortion were associated with increased mortality. Twelve patients have undergone a Fontan procedure at a mean duration after bidirectional Glenn of 18 months with 1 death (8%). The bidirectional Glenn procedure provides excellent palliation in high-risk patients and appears useful as a staging procedure before Fontan correction.

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Afterload independence and sensitivity to inotropic state.

Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.

The effects of cyanosis on myocardial blood flow, oxygen utilization, and lactate production in dogs.

To elucidate differences in myocardial blood flow and metabolism between cyanotic and normal hearts, a model of chronic cyanosis was created in five adult mongrel dogs by anastomosing the inferior vena cava to the left atrium. After 6 to 9 months, myocardial blood flow, the ratio of subendocardial to subepicardial flow, oxygen consumption, oxygen extraction ratio, and lactate consumption in these cyanotic dogs and five control dogs were determined under baseline conditions and during pharmacologic stress with isoproterenol (0.2 micrograms/kg/min). Radioactive microspheres were used to determine left and right ventricular blood flow rates, and arterial and coronary sinus differences in oxygen and lactate levels were measured. At baseline and during stress, oxygen consumption and oxygen extraction ratios were identical in control and cyanotic hearts. Total myocardial blood flow was increased with stress and did not differ between cyanotic and control hearts. Left ventricular muscle from cyanotic hearts did exhibit lower endocardial/epicardial blood flow ratios than those of control hearts at rest, and the relative subendocardial flow decreased further with stress. During isoproterenol infusion, myocardial lactate production, indicative of anaerobic metabolism, was evident in two of five cyanotic animals and none of the control dogs. The relative subendocardial ischemia and its further aggravation by stress in cyanotic hearts may contribute to the pathophysiologic basis of myocardial dysfunction in cyanotic heart disease.

Developmental changes in reperfusion injury. Comparison of intracellular ion accumulation in ischemic and cardioplegic arrest.

Developmental differences in ischemic and potassium cardioplegic arrest were evaluated in newborn (birth to 7 day old) and adult (6 to 12 month old) New Zealand white rabbit hearts isolated and perfused by Langendorff's method. An extracellular space washout technique was used to measure intracellular sodium and calcium in the two age groups after ischemia alone, after normothermic and hypothermic cardioplegia, and after cardioplegia with reperfusion. Although the intracellular ionic contents of nonreperfused adult hearts after 30 and 40 minutes of ischemia were identical, there was a twofold elevation in intracellular sodium level after 40 minutes of ischemia in the newborn hearts. Adult hearts arrested by normothermic potassium cardioplegia demonstrated no alteration in the intracellular ionic content, whereas in the newborn hearts, potassium cardioplegia produced excess intracellular calcium loading before reperfusion, which was greater than that occurring with ischemia alone. When hypothermia (12 degrees C) was combined with cardioplegic arrest, a prereperfusion influx of sodium and calcium was not observed in the newborn hearts, and ionic reperfusion injury was blunted in both newborn and adult hearts. These studies demonstrate that the newborn heart is more susceptible than the adult to both ischemia and cardioplegia. This may be due to age-dependent differences in transmembrane passive diffusion, sodium/calcium exchange, or calcium slow channel properties and suggests alternative myocardial protective strategies for the newborn infant.

Developmental changes in reperfusion injury. A comparison of intracellular cation accumulation in the newborn, neonatal, and adult heart.

Intracellular sodium and calcium accumulation were measured after 30 and 40 minutes of ischemia and 30 minutes of reperfusion in newborn (0 to 7 day), neonatal, (14 to 21 day), and adult (4 to 6 month) New Zealand white rabbit heart preparations. Newborn hearts showed twofold and threefold elevations of calcium when exposed to 30 and 40 minutes of ischemia and reperfusion, respectively, whereas sodium increase was noted only in the 40 minute group. Conversely, adult hearts exhibited sodium elevation if exposed to ischemia for 30 minutes and calcium accumulation occurred only after 40 minutes of ischemia. There was no significant alteration in intracellular sodium and calcium levels after ischemic intervals of 30 and 40 minutes in the neonate. These studies demonstrate that the immature newborn heart is the most susceptible and the neonatal heart is the least susceptible to injury sustained by ischemia followed by reperfusion. These differences in susceptibility to ischemia may be due to age-dependent alterations of intramembrane ionic pumps and channels.

Myocardial energetics after thermally graded hyperkalemic crystalloid cardioplegic arrest.

Previous studies assessing the efficacy of myoprotective regimens have compared preischemic and postischemic myocardial oxygen consumption within a limited range of cardiac performance. However, recent data suggest that ischemia-induced perturbations in myocardial energetics may occur only when the left ventricle develops physiologic pressures. Therefore, in canine hearts supported by cardiopulmonary bypass, myocardial oxygen consumption (ml oxygen X 10(-2)/beat/100 gm left ventricular weight) was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of cardioplegic arrest. The ischemic insult was graded by maintaining myocardial temperature at 12 degrees C (Group I, n = 6), 20 degrees C (Group II, n = 7), or 28 degrees C (Group III, n = 6). Postischemic Starling curves were unchanged in Groups I and II but depressed 53% in Group III hearts (p less than 0.005). In Group I, postischemic myocardial oxygen consumption at specific peak developed pressures was similar to preischemic oxygen consumption. In contrast, postischemic Group II and III hearts consumed 39% more oxygen than preischemically when peak developed pressure exceeded 75 mm Hg (p less than 0.01). Postischemic hearts demonstrated reciprocal changes in arteriovenous oxygen content difference (24%, 30%, and 34% lower than preischemic values for Groups I, II, and III, respectively) and coronary blood flow (156%, 195%, and 192% higher than preischemic values for Groups I, II, and III, respectively). Only in Group II and III hearts did the increased coronary blood flow offset the defect in oxygen extraction such that myocardial oxygen consumption was increased. These data suggest that inefficient utilization of oxygen when the heart is developing physiologic pressures is a sensitive marker for myocardial injury after crystalloid cardioplegic arrest.

Atrioventricular valve competence after takedown to improve exposure during ventricular septal defect repair.

Although the atrioventricular valve and its attachments can sometimes obscure the superior margin of a ventricular septal defect, concern for valvular competence has made surgeons hesitant to take down the atrioventricular valve. Over a 10-year period, the right atrioventricular valve was taken down to improve exposure for ventricular septal defect repair in 40 patients at our institution, and follow-up echocardiographic studies to determine the degree of valvular regurgitation were available in 32. On the basis of the area of the color flow jet, valvular regurgitation was graded as none in 22 and trivial in 10. Heart block did not develop in any patient, and there were no deaths. Takedown and resuspension of the atrioventricular valve is a safe and effective technique that improves exposure for ventricular septal defect repair and does not adversely affect valve competence.

Developmental differences in myocardial protection in response to 5'-nucleotidase inhibition.

Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible for conversion of high-energy phosphates to their the diffusible precursors, may help to explain age-related differences in tolerance of global myocardial ischemia. Postischemic function and high-energy phosphate content were measured in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month), and 6 to 12 months old (adult). Hearts in each age group were subjected to 60 minutes of ischemia at 34 degrees C either with no cardioplegia, with unmodified St. Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibitor. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pentoxifylline to St. Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total nondiffusible nucleotide levels to control values and improved recovery of cardiac output and developed pressure compared with results with unmodified St. Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the older age groups. In 1-month-old hearts, St. Thomas' Hospital cardioplegia improved recovery compared with recovery after unprotected ischemia, but no incremental improvement in function or high-energy stores was seen with addition of pentoxifylline. The lack of effect of pentoxifylline on neonatal hearts suggest that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the improved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benefits of low 5'-nucleotidase activity occurring naturally in the neonate.

The management of severe subaortic stenosis, ventricular septal defect, and aortic arch obstruction in the neonate.

Neonates with ventricular septal defect and aortic arch obstruction frequently have subaortic stenosis resulting from posterior deviation of the infundibular septum. Because the aortic anulus is often hypoplastic, making direct resection of the infundibular septum through the standard transaortic approach difficult, the optimal method of repair is uncertain. From September 1989 through November 1991, seven patients with ventricular septal defect, coarctation (n = 4), or interrupted aortic arch (n = 3) and severe subaortic stenosis underwent repair with use of a technique that included transatrial resection of the infundibular septum. Their ages ranged from 5 to 63 days (median 15 days) and weights from 1.3 to 5.4 kg (mean 3.1 kg). Only one patient was older than 1 month. The systolic and diastolic ratios of the diameter of the left ventricular outflow tract to that of the descending aorta were 0.53 +/- 0.09 mm (standard deviation) and 0.73 +/- 0.11, respectively. At operation, the posteriorly displaced infundibular septum was partially removed through a right atrial approach by resecting the superior margin of the ventricular septal defect up to the aortic anulus. The resulting enlarged ventricular septal defect was then closed with a patch to widen the subaortic area. In each patient the aortic arch was repaired by direct anastomosis. All patients survived operation; there was one late death from noncardiac causes 3 months after repair. The survivors remain well from 3 to 14 months after repair (mean 8 months). All are in sinus rhythm and none has a residual ventricular septal defect. One patient underwent successful balloon dilation of a residual aortic arch gradient late after repair. No patient has significant residual subaortic stenosis, although one has valvular aortic stenosis. This series suggests that in neonates with ventricular septal defect and severe subaortic stenosis resulting from posterior deviation of the infundibular septum, direct relief can be satisfactorily accomplished from a right atrial approach. This method provides effective widening of the left ventricular outflow tract and is superior to palliative techniques or conduit procedures.

Results of a policy of primary repair of truncus arteriosus in the neonate.

Although the early mortality for repair of truncus arteriosus has decreased in the modern era, routine correction in the neonate has not been widely adopted. To assess the results of our protocol of early repair, we reviewed 46 neonates and infants undergoing repair of truncus arteriosus at the University of Michigan Medical Center from January 1986 to January 1992. Their ages ranged from 1 day to 7 months (median 13 days) and weights from 1.8 kg to 5.4 kg (mean 3.1 kg). Repair was performed beyond the first month of life in only 8 patients, because of late referral in 7 and severe noncardiac problems in 1. Associated cardiac anomalies were frequently encountered, the most common being interrupted aortic arch (n = 5), nonconfluent pulmonary arteries (n = 4), hypoplastic pulmonary arteries (n = 4), and major coronary artery anomalies (n = 3). Truncal valve replacement was performed in 5 patients with severe regurgitation, 3 of whom also had truncal valve systolic pressure gradients of 30 mm Hg or more. The truncal valve was replaced with a mechanical prosthesis in 2 patients and with a cryopreserved homograft in 3 patients. Right ventricle-pulmonary artery continuity was established with a homograft in 41 patients (range 8 mm to 15 mm), a valved heterograft conduit in 4 (range 12 mm to 14 mm), and a nonvalved polytetrafluoroethylene tube in the remaining patient (8 mm). There were 5 hospital deaths (11%, 70% confidence limits 7% to 17%). Multivariate and univariate analyses failed to demonstrate a relationship between hospital mortality and age, weight, or associated cardiac anomalies. Only 1 death occurred among 9 patients with interrupted aortic arch or nonconfluent pulmonary arteries. Hospital survivors were followed-up from 3 months to 6.3 years (mean 3 +/- 0.4 years). Late noncardiac deaths occurred in 3 patients, all within 4 months after the operation. Actuarial survival was 81% +/- 6% at 90 days and beyond. Despite the prevalence of major associated conditions, early repair has resulted in excellent survival. We continue to recommend repair promptly after presentation, optimally within the first month of life.

Aortopulmonary fenestration with pulmonary artery septation for single ventricle and subaortic obstruction.

A neonate with functional single ventricle and severe subaortic obstruction received a palliative procedure that involved a side-to-side anastomosis of the aorta and pulmonary artery, placement of a patch in the main pulmonary artery to divide the systemic and pulmonary circulations, and creation of a small opening in the patch to provide pulmonary blood flow. The patient recently underwent a bidirectional Glenn procedure at 10 months of age. This procedure obviates the need for a modified Blalock-Taussig shunt and may provide a more reliable source of blood to promote growth of both pulmonary arteries.

Nonoperative control of retroperitoneal hemorrhage secondary to placement of an inferior vena cava occluding device in a patient with recurrent pulmonary emboli.

A woman with multiple recurrent pulmonary emboli and iatrogenic inferior vena cava perforation caused by the Hunter-Sessions introducer was treated successfully by placement of a Hunter-Sessions balloon to control the ensuing retroperitoneal hemorrhage and interrupt the inferior vena cava. Full anticoagulation therapy was continued throughout the operation and postoperatively.

Palliative arterial repair for transposition, ventricular septal defect, and pulmonary vascular disease.

Failure to repair transposition of the great arteries and ventricular septal defect in the young infant results in the early development of pulmonary vascular occlusive disease. Complete repair, preferably by an arterial switch procedure and ventricular septal defect closure, may then not be possible. We report a palliative arterial switch procedure in a 5 1/2-year-old patient with transposition, ventricular septal defect, and severe pulmonary vascular obstructive disease in whom progressive hypoxemia and exercise intolerance developed. An arterial repair without ventricular septal defect closure was performed. After the operation, the child's systemic arterial oxygen saturation and exercise tolerance have substantially improved. Although the progression of pulmonary vascular disease may not be altered, arterial repair can provide effective palliation in this subset of patients.

Intracellular sodium and calcium in the postischemic myocardium.

Intracellular sodium and calcium were measured in 30 isolated perfused rat hearts exposed to normothermic ischemic intervals varying from 0 to 40 minutes followed by 35 minutes of reperfusion. Accumulation of these elements was correlated with alterations in postischemic isovolumic contractile function. There were increases in calcium of 207%, 390%, and 681% of the non-ischemic control following reperfusion after respective ischemic intervals of 30, 35, and 40 minutes. These corresponded to decrements in peak developed pressure of 23.8% after 30 minutes, 68.6% after 35 minutes, and no recovery of function after 40 minutes of ischemia. Thirty-five and 40 minutes of ischemia produced 138% and 170% increases in intracellular sodium, respectively. These data show that there is a graded accumulation of intracellular sodium and calcium that correlates with the duration of ischemia and the degree of functional impairment in the postischemic heart. Measurement of intracellular sodium and calcium may, therefore, serve as an adjunct to other biochemical and functional factors used to quantitate postischemic and postcardioplegic damage in the development of new myoprotective regimens.

Temperature-specific effects of adjuvant diltiazem therapy on myocardial energetics following potassium cardioplegic arrest.

Adjuvant slow calcium channel blockade theoretically minimizes the calcium influx attendant to potassium-induced cardioplegic arrest, particularly if clinically acceptable levels of cardiac hypothermia are not maintained. The present study assessed the efficacy of diltiazem therapy in ameliorating perturbations of myocardial oxygen consumption that could be attributable to postischemic intracellular calcium accumulation. In 30 canine hearts, myocardial oxygen consumption was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of either 20 or 28 degrees C potassium cardioplegic arrest. The intracoronary perfusate in randomized hearts was modified by the addition of diltiazem, 150 micrograms/kg. Although systolic performance (as defined by peak developed pressure as compared with balloon volume curves) was unchanged after 20 degrees C ischemia, adjuvant diltiazem therapy prevented the 44 +/- 2% (p less than .01) decrease in peak developed pressure after 28 degrees C arrest. Moreover, the 39% augmentation of postischemic myocardial oxygen consumption at specific peak developed pressure following both 20 and 28 degrees C ischemia was attenuated with diltiazem only after the warmer ischemic interval. This difference was characterized by a larger (35 +/- 2 vs. 26 +/- 2%; p less than .025) decrease in postischemic oxygen extraction despite a comparable hyperemia. These data suggest that adjuvant diltiazem therapy during potassium-induced cardioplegic arrest preserves energy-efficient pump function only after warmer ischemia, thereby limiting the clinical application of this myoprotective regimen.

Oxygen utilization during isovolumic pressure-volume loading: effects of prolonged extracorporeal circulation and cardioplegic arrest.

In canine hearts supported by cardiopulmonary bypass, isovolumic peak developed pressure (PDP, mm Hg) and myocardial oxygen consumption (MVO2, ml O2 X 10(-2)/beat/100 gm left ventricular [LV] weight) were determined at 5-ml increments of LV balloon inflation before and after either 2 hours of potassium cardioplegic arrest (ischemia, N = 7) or a comparable period of normothermic perfusion without ischemia (control, N = 6). The sensitivity of MVO2 as a marker of ischemic injury was compared with preservation of both adenosine triphosphate (ATP) stores and systolic pump function. Over a physiological range of end-diastolic volumes (5 to 35 ml) and end-diastolic pressures (0 to 18 mm Hg), the Frank-Starling curves were not depressed following both cardioplegic arrest and prolonged nonischemic perfusion. Although ATP stores decreased by 26% and 22% (ischemia and control groups, respectively; not significant), these levels did not distinguish the effects of cardioplegic arrest from prolonged perfusion. At the preinterventional measurement in both groups, PDP between 50 and 200 correlated with MVO2 from 3.0 to 10.0 (r = +0.84). Following cardioplegic arrest, postischemic MVO2 increased 137 +/- 6% when measured over the PDP range of 75 to 200 mm Hg (p less than 0.01). This change was not evident at a PDP of less than 75, in the empty beating heart, or in control hearts subjected to nonischemic extracorporeal perfusion. These data suggest that increased utilization of oxygen to develop physiological pressures may be a more sensitive indicator of ischemic injury than shifts in the pressure-volume relationship or depletion of adenine nucleotide stores.

Pharmacologic support with high-energy phosphate preservation in the postischemic neonatal heart.

Milrinone improves function in failing adult hearts. This study examined its effect on immature myocardium. Using an isolated working neonatal rabbit heart preparation, we measured myocardial function, high-energy compounds, and cyclic adenosine monophosphate. Hearts were subjected to 1 hour of normothermic ischemia, 10 minutes of reperfusion with Ringer's solution, and 30 minutes of reperfusion with either unaltered Ringer's, Ringer's with dobutamine (0.1 microgram/mL), or Ringer's with milrinone (1 microgram/mL). These hearts were compared with each other, with a control group continuously perfused for 70 minutes, and with a group of hearts that were made ischemic and reperfused for only 10 minutes. There was a progressive decline in adenosine triphosphate levels measured in hearts from the groups receiving 10 and 40 minutes of reperfusion with unaltered perfusate, and cardiac output fell to 82% +/- 4% of preischemic control in the latter group. When either dobutamine or milrinone was added to the reperfusion solution, postischemic myocardial function was restored completely, and the loss of adenosine triphosphate with reperfusion was halted. Cyclic adenosine monophosphate level was highest in ischemic/40-minute reperfused hearts, and there was no measurable increase in cyclic adenosine monophosphate level in the group of hearts receiving milrinone. The mechanism of preservation of high-energy stores with inotropic agents is not known but may involve potentiation of mitochondrial oxidative phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Optimum treatment of discrete subaortic stenosis.

Discrete subaortic stenosis typically appears as a well-defined membrane beneath the aortic valve. To assess the merits of alternative approaches to this problem, we have reviewed the results of operations for discrete subaortic stenosis from 1978 through 1990. Excision of the subaortic membrane alone was performed in 16 patients (group I). Excision of the membrane with resection of septal muscle was performed in 24 patients (group II). The groups were similar in age at operation, duration of follow-up, and preoperative and postoperative transvalvar gradients. There were no operative or late deaths. Reoperations for recurrent subaortic stenosis were performed in 4 group I patients (25%; 70% confidence limits, 16% to 38%) and 1 group II patient (4%; 70% confidence limits, 2% to 11%). Pacemakers were inserted for postoperative complete heart block in 1 group I patient (6%; 70% confidence limits, 2% to 16%) and 2 group II patients (8%; 70% confidence limits, 4% to 16%). We conclude that muscle resection combined with membrane excision in patients with discrete subaortic stenosis does not increase the risk of death or heart block, and does lower the risk of reoperation for recurrent subaortic stenosis.

The concentration of calcium in neonatal cardioplegia.

The optimal calcium concentration in cardioplegia for the newborn has not been determined. Therefore, the effect of 0, 0.6, 1.2, 1.8, and 2.4 mmol/L calcium in modified St. Thomas cardioplegia was evaluated in isolated working hearts of 7- to 10-day-old rabbits. Functional recovery was determined by comparing aortic flow, developed pressure, and first derivative of left ventricular pressure (dP/dt) before and after 1 hour of normothermic (37 degrees C) ischemia. As percentages of baseline values, recovery of developed pressure and dP/dt averaged 10% +/- 1% (mean +/- standard error of the mean) and 10% +/- 1% with 0 mmol/L, 46% +/- 7% and 44% +/- 8% with 0.6 mmol/L, 79% +/- 2% and 76% +/- 2% with 1.2 mmol/L, 67% +/- 2% and 61% +/- 5% with 1.8 mmol/L, and 65% +/- 5% and 65% +/- 7% with 2.4 mmol/L calcium, respectively. Significant improvement in recovery of developed pressure and dP/dt was detected when the calcium concentration was increased from 0 to 0.6 mmol/L and from 0.6 to 1.2 mmol/L, but the groups with 1.2, 1.8, and 2.4 mmol/L did not differ from one another significantly in terms of developed pressure and dP/dt recovery. There was no recovery of aortic flow when 0 mmol/L calcium was used; at calcium concentrations of 0.6, 1.2, 1.8, and 2.4 mmol/L, recovery of aortic flow averaged 16% +/- 7%, 63% +/- 10%, 23% +/- 10%, and 36% +/- 11% of baseline values, respectively. Recovery of aortic flow with 1.2 mmol/L calcium was significantly higher than at concentrations of 0.6 and 1.8 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship of cimetidine to 5-hydroxytryptamine tissue levels in stress ulceration in the rat.

We studied the effect of cimetidine on 5-hydroxytryptamine (5-HT) levels in various tissues in restrained rats. Sixty male Sprague-Dawley rats, divided into four groups, received four intraperitoneal injections at 6-hour intervals in doses determined by body weight. Group I (control) was injected with saline (1 ml/300 gm) and was not restrained. Group II was injected with saline (1 ml/300 gm) and restrained for 18 hours beginning 1 hour after the first injection. Group III was injected with cimetidine (100 mg/kg) and was not restrained, whereas Group IV was injected with cimetidine (100 mg/kg) and restrained according to the schedule for Group II. The rats were killed and their stomachs were collected and graded for ulceration. 5-Hydroxytryptamine levels in the antrum and fundus of the stomach, the colon, the liver, and rectus abdominis muscle were determined by spectrophotofluorometry. Cimetidine prevented an increase in 5-HT in the antrum and protected against ulceration. As 5-HT levels in other tissues were not altered by restraint-induced stress, the phenomenon may be specific to the antrum. The protection against ulceration and elevated 5-HT levels conferred by cimetidine was comparable to that of vagotomy in similar models.