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Biomedical subjects

E D Miller

Publications and source records attributed to E D Miller.

At least 19 recordsLinked to original sources
PubMed1992

Pregnancy alters the hemodynamic responses to cocaine in the rat.

To test our hypotheses that the hemodynamic response to cocaine may be altered during pregnancy, cocaine (0.33 mg/kg/min) was infused intravenously to chronically catheterized pregnant and nonpregnant female rats. Cardiac output and regional blood flow were measured, and cocaine concentrations in plasma and tissues, as well as plasma cholinesterase activity were determined. Results were compared between pregnant and nonpregnant groups. Cocaine produced a significant decrease in heart rate, accompanied by a fall in cardiac output, and decreased cerebral, myocardial, and placental blood flow in pregnant rats. The plasma cocaine concentration in pregnant animals was lower than that of nonpregnant ones, but tissue concentrations were similar in both groups. These results indicate that pregnancy enhances cardiovascular responses to subtoxic doses of cocaine. There was little placental transfer of cocaine with a fetal to maternal plasma concentration ratio of 0.28.

Animals↗
PubMed1991

Subarachnoid blockade alters homeostasis by modifying compensatory splanchnic responses to hemorrhagic hypotension.

To demonstrate that sympathetic responses transmitted by the splanchnic nerve help maintain intravascular stability, 12 mongrel dogs (35-45 kg each), anesthetized with pentobarbital, were given two separate but identical hypotensive stimuli (mean arterial blood pressure of 60 mm Hg for 15 min) by the withdrawal of appropriate amounts of blood. The first stimulus was performed in the absence of drug or surgical manipulation. The second stimulus was performed after animals were subjected to no intervention (n = 4), bilateral splanchnic nerve section (n = 4), or spinal anesthesia (n = 4). Before and 10 min after the onset of hypotension, arterial epinephrine concentration and adrenal medullary and abdominal organ blood flow were measured. In the group without intervention, the second hypotensive stimulus (like the first) elicited 3-fold increases in adrenal medullary blood flow, 40-fold increases in arterial epinephrine concentration, and a 61% reduction in abdominal organ blood flow (P greater than 0.002). The volume of blood withdrawn to produce hypotension was similar (approximately 21 ml.kg-1). Bilateral splanchnic nerve section attenuated the adrenal medullary blood flow, arterial epinephrine concentration, and abdominal organ blood flow responses to hypotension by 86, 64, and 66%, respectively (P less than 0.008), and the blood volume withdrawn was reduced by 42% (P less than 0.02). Spinal anesthesia eliminated the adrenal medullary blood flow response to hypotension, attenuated the arterial epinephrine concentration and abdominal organ blood flow responses by 78 and 57%, respectively (P less than 0.01), and decreased the blood volume extracted by 55% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1979

Converting-enzyme activity and pressor responses to angiotensin I and II in the rat awake and during anesthesia.

Plasma renin activity (rate of angiotensin I generation) does not increase during anesthesia with ketamine, fluroxene, halothane or enflurane in the sodium-repleted rat. However, blood pressure decreases when an angiotensin II antagonist, saralasin, is administered during halothane or enflurane anesthesia, but not during ketamine or fluroxene anesthesia. Differences in the rates of conversion of angiotensin I to angiotensin II induced by various anesthetic agents could help explain these previous findings. To determine the effects of anesthetic agents on angiotensin I conversion, experiments were performed in vitro and in vivo. The activities of rabbit pulmonary converting enzyme in the presence and absence of halothane or fluroxene were measured as rates of appearance of the dipeptide, histidyl-leucine, a product of angiotensin I hydrolysis to angiotensin II. Halothane and fluroxene did not alter conversion. Infusions of angiotensin I and angiotensin II were given to Wistar rats to construct dose-blood pressure response curves. The animals were then anesthetized with ketamine or halothane and infusions were repeated. Angiotensin I and angiotensin II induced similar blood pressure responses in awake and anesthetized rats. However, ketamine accentuated the pressor responses to angiotensin I and angiotensin II, whereas halothane depressed the responses. With the anesthetic agents studied, there is no significant effect on conversion of angiotensin I to angiotensin II either in vitro or in vivo.

Angiotensin I↗
PubMed1979

Indices of myocardial oxygenation during coronary-artery revascularization in man with morphine versus halothane anesthesia.

A prospective study in 12 adult male patients undergoing coronary-artery revascularization was conducted to compare the effects of a morphine versus a halothane anesthetic technique on several indices of myocardial oxygen supply and demand. Indices reflecting myocardial contractility, preload, afterload, and heart rate were measured. Undesirable increases in systemic and pulmonary capillary wedge pressure were minimized using sodium nitroprusside as needed. In the period after sternotomy but before revascularization, patients anesthetized with morphine (mean 2.1 mg/kg) had significant (P less than .05) increases in rate-pressure product, tension-time index, blood pressure, and heart rate, as well as relative myocardial ischemia, evidenced by significant ST-segment depression in the V5 lead of the EKG and a decreased diastolic pressure-time index/tension-time index compared with patients anesthetized with halothane (mean .75 per cent inspired). Few difficulties associated with myocardial depression were seen in patients anesthetized with halothane. Halothane, at least in a well-monitored environment, is safe for use in patients without severe ventricular dysfunction undergoing coronary-artery revascularization.

Anesthesia, General↗
PubMed1979

Renin response to hemorrhage in awake and anesthetized rats.

Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.

Animals↗
PubMed1978

Blood pressure support during general anesthesia in a renin-dependent state in the rat.

Previous work had shown that halothane and enflurane at 1 MAC and ketamine, 125 mg/kg, did not increase plasma renin activity (PRA) in the normal sodium-replete rat. To investigate the renin-angiotensin system with increased PRA, 25 rats were fed a low-sodium diet for five to seven days and divided into four groups: awake; halothane, 1.26 vol per cent; enflurane, 1.75 vol per cent; ketamine, 125 mg/kg, intramuscularly. The protocol consisted of a two-hour awake period, then an hour of stable anesthesia, followed by 30 min infusion of saralasin, an angiotensin II competitive inhibitor. An additional 18 rats had PRA measured by radioimmunoassay before and after an hour of stable anesthesia. Stable anesthesia decreased mean arterial pressure from 122 +/- 2 to 69 +/- 4 torr for the halothane group, 70 +/- 3 torr for the enflurane group, and 103 +/- 7 torr for the ketamine group. When saralasin was infused for 30 min, blood pressure decreased to 100 +/- 3 torr for the awake group, 40 +/- 1 torr for the halothane group, 44 +/- 2 torr for the enflurane group, and 73 +/- 3 torr for the ketamine group. PRA increased from 4.3 +/- 0.5 ng/ml/hr for sodium-replete rats to 12.9 +/- 1.7 ng/ml/hr for sodium-depleted rats. After an hour of stable anesthesia, PRA increased in all the anesthetized groups. The authors conclude that the anesthetic agents studied increase renin release in the sodium-depleted rat. The initial renin level may be important in determining whether changes in renin release occur with anesthetic agents.

Anesthetics↗
PubMed1978

Sodium cyanide antagonism of the vasodilator action of sodium nitroprusside in theisolated rabbit aortic strip.

Resistance to sodium nitroprusside (SNP) is uncommon, but its occurrence has led to massive overdoses of SNP and sometimes death. To examine the mechanism responsible for resistance, aortic smooth muscle strips were prepared and dose-response curves for norepinephrine (NE) obtained. SNP alone caused a shift of the dose-response curve for NE to the right. However, this shift was less when the strips were exposed to both SNP and sodium cyanide (CN-). When CN- alone was added to the aortic strips, the response to NE was unchanged. In a further group of aortic muscle strips first contracted with NE and then relaxed with SNP, the addition of CN- caused the muscles to contract again. It is concluded that CN- antagonizes the action of SNP in vitro, and that this antagonism is specific for SNP.

Animals↗
PubMed1976

Renin--angiotensin antagonists and the regulation of blood pressure.

The role of the renin--angiotensin system in the regulation of blood pressure in dogs and in human subjects was assessed by the use of the nonapeptide converting enzyme inhibitor (CEI), permitting the following conclusions: 1) In the normal, sodium replete dog, the renin--angiotensin system plays little role in the regulation of blood pressure. 2) As sodium depletion progresses, the renin--angiotensin system becomes increasingly important in the maintenance of blood pressure. In the markedly hypovolemic animal, blocking the conversion of angiotensin I to angiotensin II leads to prolonged hypotension of shock-like levels. 3) The renin--angiotensin system is responsible for the initiation of renovascular hypertension. Blood pressure does not rise during chronic renal artery constriction when the generation of angiotensin II is prevented by the CEI. Although angiotensin II is essential for the initiation of the elevated blood pressure, the renin--angiotensin system plays a decreasing role in the maintenance of the chronic hypertension as sodium and water are retained, and plasma volume increases. 4) In congestive failure induced in the conscious dog by circulatory impairment, the renin--angiotensin--aldosterone system plays an essential role in the compensatory response. During chronic administration of the CEI, the animal cannot compensate even for a relatively mild degree of constriction, and remains hypotensive. In the dog with congestive failure, as in the dog with renovascular hypertension, plasma renin activity (PRA) and plasma aldosterone are elevated early in the syndrome; during this phase, injection of the nonapeptide produces a marked drop in blood pressure. With the retention of sodium and water, and expansion of plasma and extravascular fluid volumes, PRA and plasma aldosterone return to control levels in the new steady state. The inhibitor no longer produces a drop in blood pressure. Thus, the sequential changes in the renin--angiotensin--aldosterone system are remarkably similar in renovascular hypertension and congestive failure. 5) In the normal, salt replete human subject the renin--angiotensin system plays little role in the regulation of blood pressure either in the recumbent or upright posture. However, with relatively mild sodium depletion, the CEI transiently lowers blood pressure even in the recumbent subject. In the absence of angiotensin II such sodium-depleted subjects are unable to compensate when tilted upright, and faint within minutes.

Adrenalectomy↗