Deliberate hypotensive epidural anesthesia for patients with normal and low cardiac output

The use of hypotensive anesthesia is contraindicated in patients with ventricular dysfunction, even though afterload reduction often improves ventricular performance. The purpose of this study was to prospectively assess systemic hemodynamic responses to deliberate hypotension with epidural anesthesia in patients with chronic left ventricular dysfunction. Hemodynamic measurements were performed in 29 patients undergoing total hip arthroplasty under deliberate hypotensive epidural anesthesia using low-dose intravenous epinephrine infusion to maintain mean arterial pressure (MAP) at 50-60 mm Hg. Intraoperative MAP decreased from 100 +/- 16 to 56 +/- 9 mm Hg by 30 min after epidural injection (P < 0.0005). Concurrently, cardiac index (CI) increased from a preanesthetic baseline value of 2.9 +/- 0.5 to 3.3 +/- 0.9 L.min-1.m-2 at 30 min (P < 0.005) after epidural injection and stroke volume index (SVI) increased from 41 +/- 8 to 50 +/- 14 mL.beat-1.m-2 30 min after epidural injection (P < 0.005). Heart rate and central venous and pulmonary artery diastolic pressures were maintained under hypotension with epidural anesthesia in all patients. During deliberate hypotension with epidural anesthesia, patients with a history of congestive heart failure or low preanesthetic CI (< or = 2.5 L.kg-1.m-2) increased their CI and SVI into the normal range. There were no significant perioperative complications in either of these groups. Hypotensive epidural anesthesia can be used successfully in patients with low cardiac output from ventricular dysfunction undergoing total hip arthroplasty.     

Pulmonary shunting during anesthesia with deliberate hypotension

Pulmonary shunting (Qs/Qt with FIO2 = 1) was measured in 18 anesthetized patients during deliberate hypotension. Hypotension was induced in 12 patients with sodium nitroprusside and light halothane anesthesia and in six others with deep halothane anesthesia and mechanical hyperventilation. Similar results were observed in the two groups. During the hypotensive period mean arterial pressure (MAP) was reduced to 49 +/- 2 torr, a 37 per cent decrease from the control level after the onset of operation and a 40 per cent decrease compared with the recovery level during closure of the wound. Qs/Qt, however, remained unchanged throughout the study: 5.2 +/- 0.9 per cent initially, 5.4 +/- 0.8 per cent during hypotension, and 4.7 +/- 0.5 per cent during recovery. It is concluded that pulmonary shunting need not develop during deliberate hypotension induced with either technique.     

Prevention of hypotension during spinal anaesthesia for caesarean section: ephedrine infusion versus fluid preload

We compared the efficacy of prophylactic ephedrine infusion over fluid preloading in prevention of maternal hypotension during spinal anaesthesia for Caesarean section. Forty-six women undergoing elective Caesarean section at term were allocated randomly to receive either intravenous fluid preloading with Hartmann's solution 20 ml.kg-1 (fluid group) or prophylactic intravenous ephedrine 0.25 mg.kg-1 (ephedrine group). Moderate hypotension was defined as > or = 20% reduction in systolic blood pressure and severe hypotension as > or = 30% reduction in systolic blood pressure. Maternal uterine circulation was measured using Doppler ultrasound in 11 parturients before and after spinal anaesthesia. There was a lower incidence of severe hypotension in the ephedrine group compared with the fluid group (35% vs. 65%, p = 0.04), although the incidence of moderate hypotension was similar. Mean umbilical venous pH was higher in the ephedrine group than in the fluid group (7.33 vs. 7.29, p = 0.02) and the number of patients shivering was lower in the ephedrine group (2 vs. 9, p = 0.02). No difference was found between pre- and postspinal uterine artery pulsatility indices in either group. We conclude that prophylactic ephedrine infusion alone is at least as good as fluid preload alone in combating the hypotension associated with spinal anaesthesia for Caesarean section.     

Induced hypotension during anesthesia with special reference to orthognathic surgery

Since Gardner first used arteriotomy during anesthesia to improve visibility in the surgical field, various techniques and pharmacological agents have been tried for the same purpose. With reports documenting the spread of acquired immune deficiency syndrome through blood transfusions, prevention of homologous blood transfusions during surgery has also become a major concern. Induced hypotension has been used to reduce blood loss and thereby address both issues. In orthognathic surgery, induced hypotension during anesthesia has been used for similar reasons. It is recommended that hypotensive anesthesia be adjusted in relation to the patient's preoperative blood pressure rather than to a specific target pressure and be limited to that level necessary to reduce bleeding in the surgical field and in duration to that part of the surgical procedure deemed to benefit by it. A mean arterial blood pressure (MAP) 30% below a patient's usual MAP, with a minimum MAP of 50 mm Hg in ASA Class I patients and a MAP not less than 80 mm Hg in the elderly, is suggested to be clinically acceptable. Various pharmacological agents have been used for induced hypotension during orthognathic surgery. In addition, there are many drugs that have been used in other types of surgery that could be used in orthognathic surgery to induce hypotension. Recent reports using control groups do not show significant differences in morbidity and mortality attributable to induced hypotension during anesthesia. Appropriate patient evaluation and selection, proper positioning and monitoring, and adequate fluid therapy are stressed as important considerations in patients undergoing induced hypotension during orthognathic surgery.     

Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program

BACKGROUND: Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups. METHODS AND RESULTS: With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent 4-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of >/=20 mm Hg or in diastolic blood pressure of >/=10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation. CONCLUSIONS: Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men.     

Renin response and angiotensinogen control during graded hemorrhage and shock in the dog

Hemorrhage and hemorrhagic hypotension have been shown to be potent stimulators of renin release. However, the relationship between angiotensinogen consumption and angiotensinogen production has yet to be completely defined during this type of circulatory stress. Peripheral renin activity increased progressively as the blood pressure was decreased stepwise by hemorrhage to 50 mmHg and remained elevated throughout the shock phase of the experiment. Angiotensinogen did not change from control (809 ng/ml) throughout hemorrhabic hypotension and shock. During hemorrhagic hypotension, with the infusion of the angiotensin antagonist, [1-sarcosine, 8-alanine]angiotensin II, angiotensinogen concentration fell progressively from 693 to 208 ng/ml at 50 mmHg. Intravenous angiotensin II infused continuously after the mean blood pressure reached 50 mmHg significantly elevated plasma angiotensinogen concentration. In conclusion, during hemorrhagic hypotension and shock, the kidney and the liver appeared capable of maintaining elevated plasma renin activity and adequate plasma renin substrate, angiotensinogen, respectively. The mechanism responsible for the maintenance of plasma angiotensinogen is suggested to involve a positive-feedback effect of angiotensin II on the liver.     

Prevalence, predisposing factors, and prognostic importance of postural hypotension

OBJECTIVES: To determine the prevalence and predisposing factors of postural hypotension and to evaluate the effect of postural hypotension on 10-year vascular mortality in an elderly population. METHODS: A random sample of 480 subjects aged 65 years or older was obtained in 1982. The participation rate of the subjects in the study was 72%, for a total of 347 subjects. Orthostatic testing and continuous ambulatory electrocardiographic recording, as well as comprehensive clinical evaluation, including medical history, physical examination, standard electrocardiography, chest radiography, blood pressure measurement, routine biochemical analysis, and determination of body mass index, were performed. In 1992, the 10-year mortality of subjects and causes of death were recorded from the mortality statistics. Of the participants, 184 (53%) had died and 163 were still alive. To determine the effect of postural hypotension on the 10-year mortality, the subjects who were alive and those who had died of vascular or nonvascular causes were compared. All of the examinations had been completed in 156 subjects who were still alive, in 109 subjects who had since died of vascular causes, and in 64 subjects who had died of nonvascular causes. RESULTS: An abnormal postural systolic blood pressure drop (-20 mm Hg or less) after standing for 3 minutes was demonstrated in 28.0% of subjects. There were no sex or age differences between the subjects with and without postural hypotension. No predisposing factors for postural hypotension other than elevated blood pressure were found. Chronic cardiovascular diseases, disability, body mass index, medication, and abnormal findings in ambulatory electrocardiographic monitoring were not associated with postural hypotension. In the univariate analysis, the extent of systolic or mean blood pressure change predicted neither vascular nor nonvascular death during the 10-year follow-up. On the other hand, diastolic blood pressure drop, in particular after standing for 1 minute, was associated with increased vascular mortality (odds ratio, 2.7; 95% confidence interval, 1.3 to 5.6). In the multivariate analysis, however, this association disappeared. CONCLUSIONS: Postural hypotension was common in an unselected elderly population. No predisposing factors for postural hypotension other than elevated blood pressure were found. The 10-year follow-up showed that postural diastolic, but not systolic, blood pressure drop predicted excess vascular mortality. However, this association disappeared in the multivariate analysis, thus being related to background factors such as cardiovascular diseases.     

Augmentation of blood flow through cerebral collaterals by inhibition of nitric oxide synthase

We examined the influence of nitric oxide (NO) on normal and collateral cerebral blood flow after occlusion of the middle cerebral artery (MCA). Effects of NG-nitro-L-arginine (nitroarginine), an inhibitor of NO synthase, were examined during normotension and hypotension (arterial pressure, 50 mm Hg) in 49 anesthetized dogs. Following a craniotomy, a branch of the MCA was cannulated, and collateral-dependent tissue was identified using the shadow-flow technique. Regional cerebral blood flow was measured with microspheres, and pial artery pressure was measured with a micropipette. Intravenous nitroarginine reduced blood flow to normal cerebrum by approximately 40% (p < 0.05) during normotension and hypotension, with aortic pressure maintained constant after nitroarginine administration. Injection of nitroarginine during hypotension, without control of pressor effects, increased aortic and pial artery pressure approximately twofold. Concurrently, blood flow to normal cerebrum decreased (p < 0.05), while flow to collateral-dependent cerebrum increased (p < 0.05). Phenylephrine was infused during hypotension to increase arterial pressure to values similar to those achieved following nitroarginine. Blood flow to collateral-dependent cerebrum increased (p < 0.05), but flow to normal cerebrum was not altered during infusion of phenylephrine. Thus, inhibition of NO synthase during hypotension increases arterial pressure, decreases blood flow to normal cerebrum, and increases blood flow to collateral-dependent cerebrum. Phenylephrine also increases perfusion pressure and blood flow to collateral-dependent cerebrum, but in contrast to nitroarginine, it does not redistribute blood flow from normal cerebrum.     

Lewis (FUT3) genotypes in two different Chinese populations

BACKGROUND: In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. METHODS: Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. RESULTS: The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. CONCLUSION: As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.     

Release of renal prostaglandins during endotoxin-induced hypotension

The appearance of prostaglandins in dog's blood during endotoxin-induced hypotension was studied by use of the dialysis modification of the blood bathed organ technique. An increase in prostaglandins, mainly E2 and F2alpha was found in renal venous blood, whereas no such increase was seen in blood from the abdominal aorta, the inferior vena cava or the femoral vein. Three possible trigger mechanisms for this increase i.e. hypotension, reduced flow and reflexogenic sympathetic stimulation, have been investigated. It is suggested that, in addition to these three factors, circulating hormones such as noradrenaline, angiotensin or bradykinin, play a role in this release mechanism. Administration of indomethacin produced a restoration of the systemic blood pressure to its pre-endotoxin value; concomitantly a disappearance of the prostaglandins from the circulation was observed. It is concluded that prostaglandins contribute to the hypotension induced by endotoxin. Whether they are beneficial or detrimental remains to be resolved.     

Provocation of postural hypotension by insulin in diabetic autonomic neuropathy

The effect of insulin administration on blood pressure has been investigated in eight diabetes with autonomic neuropathy. Systolic and diastolic pressures fell considerably after insulin in all of them. This effect was aggravated by tilting to the vertical position. Five patients fainted when upright with systolic blood pressures less than 50 mm. Hg. This hypotensive effect of insulin occurs whether it is administered intravenously, intramuscularly, or subcutaneously. The onset of the effect is almost immediate after intravenous insulin, is progressive, and may last for several hours. It coincides with a falling blood glucose level and occurs before hypoglycemic levels are reached, and it may be present when the blood glucose level is still elevated. Diurnal variations of postural hypotension have been recorded in some patients, the standing blood pressure falling with the onset of insulin action and rising again as the latter declines. Some of our patients were unable to differentiate between symptoms of hypoglycemia and hypotension. Postural hypotension may account for some episodes of sudden loss of consciousness without warning, usually attributed to hypoglycemia.     

Fatal intoxication with amlodipine

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.     

An approach to the treatment of essential hypertension

The efficacy and side effects of the combined administration of propranolol and phenoxybenzamine were examined in 19 patients with moderate and moderately severe essential hypertension. By titrating the dosage of both drugs against pulse rate and blood pressure response, propranolol was given between 80 and 160 mg. and phenoxybenzamine between 20 and 50 mg. per day in divided doses. There was a substantial reduction in both systolic and diastolic blood pressure in both recumbent and upright positions without orthostatic hypotension. Normal blood pressure (140/90 mm. Hg or less) or near normal (150/100 mm. Hg or less) was attained in 14 of the patients in the recumbent and 17 in the upright position. Pulse rate also decreased significantly, whereas body weight increased but not significantly so. Except for a reduction of ejaculation in three out of six male subjects, no symptomatic side effects were detected, and no changes in the liver or renal function or in blood count were observed. Despite the short duration of therapy, 3 to 10 weeks, this study clearly demonstrates that propranolol and phenoxybenzamine given together in individualized doses are very effective in lowering arterial blood pressure with minimal side effects.     

Hemodynamic mechanism of vasovagal syncope

Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. Thirty two patients with recurrent unexplained syncope were studied using a head-up (60 degrees) tilt test. The electrocardiogram, arterial blood pressure, pulmonary arterial pressure and central venous pressure were monitored continuously, and the cardiac output was measured by the thermodilution method. Twenty patients (62.5%) had positive tilt test responses, of which 12 developed typical vasovagal syncope with marked hypotension and bradycardia; the others developed hypotension without bradycardia. There were five women and seven men with a mean age (+/- SD) of 53.3 +/- 15 years. The effect of head-up tilt resembled that of hypovolemia. The central venous pressure, pulmonary capillary wedge pressure and cardiac output declined with an increase of heart rate and systemic vascular resistance. However the mean blood pressure was maintained. During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.22 +/- 0.43 to 1.51 +/- 0.32 liters/min/m2 (p value < 0.05) and the systemic vascular resistance index decreased from 3,689 +/- 859 to 1,999 +/- 543.9 dynes s cm5/m2 (p value < 0.05). The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.     

Comparison of hypertonic saline solutions and dextran in dialysis-induced hypotension

The efficacy of three hypertonic saline solutions for treating dialysis-induced hypotension in a randomized, blinded, crossover clinical trial of 10 patients (a minimum of three cycles per solution) was compared. Dialysis-induced hypotension, defined as a decrease in systolic blood pressure of at least 10 mm Hg or systolic blood pressure less than 100 mm Hg, was treated with an iv bolus of either 10 mL of 23% saturated hypertonic saline, 30 mL of 7.5% hypertonic saline, or 30 mL of 7.5% saline with 6% dextran 70, each containing similar osmolar loads of 80, 80, and 100 mosM, respectively. All three solutions raised systolic blood pressure within 5 min (mean pretreatment systolic blood pressure, 87 mm Hg; mean posttreatment systolic blood pressure, 101 mm Hg; P < 0.05). The magnitude of the increase was greater with saturated hypertonic saline (15 mm Hg) and dextran 70 (17 mm Hg) compared with that with hypertonic saline (9 mm Hg; P < 0.05). At 10 min, dialysis-induced hypotension was less frequent with saturated hypertonic saline (incidence, 9%) compared with hypertonic saline (45%). Beyond 10 min, however, there was a trend toward a lower incidence of further dialysis-induced hypotension with dextran 70. There were no side effects. Given equal osmole loads, the more concentrated solution produced a greater increase in systolic blood pressure. The addition of an oncotic agent such as dextran may prolong the blood pressure response beyond 10 min. It was concluded that hypertonic saline solutions safely and effectively treat dialysis-induced hypotension.     

Cause of hypotension during spinal anesthesia--the relation between the level of anesthesia and the hypotension

A retrospective study was conducted on the cause of hypotension during spinal anesthesia and also on the relation between the level of anesthesia and the hypotension. Two hundred twenty three patients who had received spinal anesthesia for gynecological surgery were divided into two groups. Group I consisted of 87 patients with a significant decrease in blood pressure, while group II consisted of 136 patients with no significant decrease in blood pressure. First, the age, dosage of spinal anesthesia, amount of preoperative transfusion, and level of spinal anesthesia were reviewed and compared between the group I and II. Next, all the patients were classified by the level of spinal anesthesia, and the degree of decrease in blood pressure and the frequency of a significant decrease in blood pressure were examined by each level of spinal anesthesia. Only the level of spinal anesthesia was found to differ significantly between the group I and II. The degree of hypotension was greater at higher levels of spinal anesthesia. More than 50% of the patients with T5 or higher levels of anesthesia had a significant decrease in blood pressure. We conclude that the cause of the significant decrease in blood pressure during high spinal anesthesia is in most part due to the blockade of the cardiac sympathetic nerve.     

Evaluation of the therapeutic efficacy of delayed-action diltiazem in the treatment of mild and moderate hypertension, with ambulatory of blood pressure monitoring

PURPOSE: To evaluate the behaviour of 24 hour blood pressure and the therapeutic efficacy of diltiazem 240mg (slow release) in mild and moderate hypertension. METHODS: In an open noncomparative study 20 hypertensive patients were evaluated after two weeks of wash out and eight weeks of therapy. Diltiazem 240mg, slow-release, was used in once a day basis. The blood pressure was evaluated through casual measures and by ambulatorial (ABPM) blood pressure monitorization. RESULTS: Sixteen patients (80%) reached therapeutic success (PAD nomalization or at least a reduction of 10mmHg), after six weeks of therapy. There were no changes in heart rate nor orthostatic hypotension. The mean reduction for the systolic blood pressure (PAS) was the 19.25mmHg and for PAD 11.60mmHg. The variables identified in ABPM (systolic and dyastolic load, SBP and DBP) showed significant reduction with maintenance of the circadian rhythm. CONCLUSION: Diltiazem 240mg, slow release, showed significant reduction (therapeutic success = 80%) in blood pressure of mild and moderate hypertensive patients associated with excellent tolerability. The circadian rhythm has been kept. The variables measured by ABPM were significantly reduced. Diltiazem demonstrated to be an important alternative for the treatment of mild to moderate hypertension due to its beneficial therapeutic effects associated to the once daily dosage.     

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

Effect of high dosages of fentanyl and piritramide upon haemodynamics, coronary blood flow and myocardial oxygen consumption (author's transl)

High dosages of narcotic analgesics are frequently utilized as the sole anaesthetic agents for patients requiring open-heart surgery. The purpose of this study was to investigate the effect of high dosages of fentanyl and piritramide upon the cardiovascular system. In anaesthetized dogs (N2O:O2=2:1; 0.5 vol% halothane) 0.03 mg/kg fentanyl (=8) and 1.5 mg/kg piritramide (n=8) respectively were given intravenously as a bolus. After the administration of fentanyl there was a slight decrease in blood pressure (10%). The hypotension was the result of a decrease in cardiac output (thermodilution technique) by 13% due to bradycardia. Total peripheral resistance and myocardial contractility remained unaffected. Similar effects were only found late after injection of piritramide, since there was an initial cardiovascular response to piritramide characterized by a marked fall in blood pressure (29%). The major cause of arterial hypotension was peripheral vasodilatation. Load data and the decrease in max dp/dt however indicated also a slight myocardial depression. The altered haemodynamics led to a decrease in myocardial oxygen consumption with both narcotics, which was nearly paralleled by a reduction in coronary blood flow. The narrowing of arteriovenous oxygen difference of the heart proved coronary dilatatory properties of fentanyl and especially of piritramide. This study indicated that high dosages of fentanyl have advantages in comparison to high dosages of piritramide. The clinical implications of the results are discussed.     

Effects of dihydropyridine Ca blockers on the renal function in nephrotic spontaneously hypertensive rat (SHR)

An animal model having both hypertension and reduced renal function was produced by intraperitoneal injection of puromycin aminonucleoside (PAN) in spontaneously hypertensive rat (SHR). Using this model, two different dihydropyridine Ca blockers, CS-905 and nicardipine, were compared with regard to the relationship between hypotensive effects and changes in renal function in a conscious state. A single oral administration of CS-905 or nicardipine at doses of 3 or 10 mg/kg produced a dose-dependent decrease in blood pressure and an increase in heart rate. Glomerular filtration rate (GFR) was decreased only at 10 mg/kg. However, there was a substantial difference between the two drugs with respect to the relationship between blood pressure and GFR. The decrease of GFR by nicardipine was observed when blood pressure was at the lowest level, while GFR decreased by CS-905 returned to the initial level when blood pressure reached a nadir. Percent decrease of GFR by CS-905 was significantly less than that by nicardipine although both agents produced almost the same degree of peak hypotension. These results suggest the decrease in GFR by Ca blockers depends not only on the degree of hypotension but other factors as well, such as the rate of blood pressure lowering. Despite the hypotension, both agents produced a marked natriuresis. Since the natriuresis was not accompanied by an increase in GFR, it was assumed that the natriuretic effect of Ca blockers stemmed from their tubular effects rather than glomerular ones.