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Biomedical subjects

R L Hamlin

Publications and source records attributed to R L Hamlin.

At least 73 records · Page 4Linked to original sources

Nutrition and the heart.

Nutritional deficiencies (e.g., carnitine in dogs, taurine in cats) resulting in cardiomyopathy, and nutritional excesses (e.g., calories leading to obesity, sodium leading to hypertension) have emerged as important considerations in cardiology. These dietary factors may become particularly exaggerated in altered physiological and/or pathological states (e.g., pregnancy, old age, primary cardiovascular disease). Unfortunately, we do not have complete information on requirements for essential nutrients, nor do we know the precise role nutrition may play in the production of so-called old-age diseases or on the interactions among other organ systems (e.g., kidney, liver) and the heart.

Animals↗

Estimating the duration of ventricular fibrillation.

As the duration of time between the onset of ventricular fibrillation and the application of defibrillation (downtime) increases, the rate of successful resuscitation decreases. Results of recent animal studies suggest that the rate of successful resuscitation may be increased after a prolonged cardiorespiratory arrest when pharmacologic therapy is instituted before defibrillation. An accurate estimation of downtime could be critical in selecting the most appropriate therapeutic intervention. The purpose of our study was to determine whether changes in the frequency or amplitude of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate downtime. We characterized the dynamics of both total power and frequency distribution of the power in the ECG during ventricular fibrillation in 11 swine to determine whether enough information existed in either parameter to estimate downtime. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic, repeatable pattern. However, median frequency showed less intersubject variability than did total power. A mathematical model of median frequency was developed and used with data obtained from ten additional swine to estimate downtime. The model estimated downtime to within 1.3 minutes of actual downtime between one and ten minutes of ventricular fibrillation. Our study has identified a new, potentially useful parameter for studying various management strategies in ventricular fibrillation as a function of downtime.

Animals↗

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR.

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of direct mechanical ventricular assistance on myocardial hemodynamics during ventricular fibrillation.

Direct mechanical ventricular assistance (DMVA) is a method of biventricular circulatory support that employs a pneumatic device to apply both systolic and diastolic forces directly to the ventricular myocardium. This study investigated the effects of DMVA on myocardial hemodynamics when applied after a prolonged cardiopulmonary arrest. Seven swine weighting 28.3 +/- 2.5 kg were instrumented for regional myocardial blood flow (MBF) measurements using tracer microspheres. Ventricular fibrillation was then induced. After 10 min of ventricular fibrillation, CPR was initiated for 3 min. DMVA was then applied through median sternotomy. Defibrillation was attempted after 3.5 min of DMVA. If unsuccessful, DMVA was instituted for another 17.5 min and a subsequent defibrillation attempt was made. Arterial oxygen content (CaO2), coronary sinus oxygen content (CcSO2), myocardial oxygen delivery/consumption (mDO2/mVO2), extraction ratio (ER), and endocardial/epicardial blood flow ratio (EN/EP) were determined during CPR, during the initial application of DMVA (DMVA1), and after the subsequent 17.5 min of DMVA in those animals not initially defibrillated (DMVA2). Three of the seven animals were successfully defibrillated during DMVA1. After the additional 17.5 min of DMVA, only one other animal was defibrillated. There was a significant improvement in CaO2, CcSO2, MBF, mDO2, mVO2, ER, and EN/EP after DMVA1 compared to CPR. Only mVO2 and ER improved significantly after DMVA2. These findings support the concept that physical diastolic augmentation may improve myocardial hemodynamics when DMVA is applied during cardiac arrest.

Animals↗

Capillary basement membrane thickness and capillary density in sedentary and trained obese Zucker rats.

The purpose of this study was to determine whether the obese Zucker rat (OZR) develops diabeteslike peripheral vascular disease and evaluate the effects of exercise training (treadmill running, 15 m/min, 17% grade, 60 min/day, 5 days/wk, for 6 or 12 wk) on skeletal muscle vascular disease. Capillary density (CD) and capillary basement membrane (CBM) thickness were measured in the plantar muscle of sedentary and trained OZR and sedentary lean Zucker rats (LZRs). At 11 wk old, when profoundly obese, hyperinsulinemic, and insulin resistant, OZRs had lower CD and thicker CBM than LZRs. These characteristics are consistent with the expression of human diabetic microangiopathy and imply altered diffusion capacity due to increased diffusion distance and changes in the capillary wall. Between 11 and 18 wk of age, OZRs became hyperglycemic. No age-related changes in CD were observed in lean or obese animals, and OZRs had lower CDs than LZRs at 18 wk of age. CBM thickness decreased from 11 to 18 wk of age in both lean and obese animals, but the decline was proportionally greater in OZRs, and the CBM of obese animals was only slightly thicker than in lean 18-wk-old animals. Exercise training did not alter CD or CBM thickness in 11-wk-old animals. In contrast, training for 6 or 12 wk increased both CD and CBM thickness in 18-wk-old animals, normalizing CD but further increasing CBM thickness relative to LZRs. Correlational analysis revealed that CBM thickness is related to basal insulin concentration (r = .29, P less than .05) but not to basal glucose (r = .12, P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Studies to determine the optimal dose of medetomidine for the dog.

This study was designed to determine optimal doses of medetomidine which, when given intravenously or intramuscularly, produce analgesia/anesthesia or tranquility in dogs. Forty-eight mature, mongrel, healthy dogs weighing between 5 and 40 kg were randomized to one of four categories according to the dose of medetomidine given: zero, low, medium, high. Low dose was 280 micrograms/m2* given i.v. or 375 micrograms/m2 given im Medium dose was 750 micrograms/m2 given iv or 1000 micrograms/m2 given im High dose was 1220 micrograms/m2 given iv or 1625 micrograms/m2 given im Dogs were given the compound iv; then at least 2 weeks (100 half-lives) later, it was given i.m. Parameters measuring analgesic/anesthetic effects or ataractic effects were monitored during a control period, and at 1/4, 1/2, 1, 2, 3, 4, 5, and 6 h after dosing. A positive (ideal) response was determined by comparing a score based upon the parameters measured to observations of an ideal response made by the investigators. The numbers of dogs, receiving each dose that manifested ideal responses at 1/2 h and returned to normal enough to be left unattended at 3 h, were determined; and the optimal dose was based upon the lowest dose that produced the desired response and the highest dose that permitted the dogs to be left unattended by 3 h. Doses of medetomidine of 750 micrograms/m2 given i.v. and 1000 micrograms/m2 given i.m. were considered to be optimal of the 3 non-zero doses used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Training-induced vascular and metabolic adaptations in normo(11 week)- and hyper(18 week)-glycemic obese Zucker rats.

The purpose of this study was to investigate the peripheral vascular and metabolic adaptations induced by aerobic training in normoglycemic (11-week-old) and hyperglycemic (18-week-old) insulin-resistant male obese Zucker rats (OZR). OZR were treadmill trained 6-11 (T6-11), 11-18 (T11-18), or 6-18 (T6-18) weeks of age at 15 m/min. 17 percent grade, 1 hour/day, 5 days/week. Forty-eight hours after the last training session and after a 12 hour fast, a tail vein blood sample was obtained for analysis of glucose and insulin concentrations, cholesterol, and glycosylated hemoglobin fraction. Glucose uptake and hindlimb vascular resistance were measured during extracorporeal perfusion of the hindlimb (1.0mU insulin/ml). Trained animals were compared to sedentary age-matched obese (S-OZR) and lean (LZR) animals. S-OZR were hyperinsulinemic and obese at 6 weeks of age, mildly hypercholesterolemic and hyperglycemic at 11 weeks, and profoundly hyperglycemic at 18 weeks. Training did not affect body weight or serum cholesterol. Fasting insulin and glucose concentrations were not different between sedentary and trained OZR, except T6-18 which had higher insulin and lower glucose concentrations. The insulin/glucose ratio was lower in OZR animals and was not altered by 6-7 week training (T6-11, T11-18), but was normalized by 12 week training (T6-18). No significant differences in glycosylated hemoglobin fractions were observed between groups. Normalization of glucose uptake was observed in trained 11-week-old OZR, and a statistically non-significant (P = 0.10) 40 percent improvement was observed in trained 18-week-old OZR. Hindlimb vascular resistance was elevated in the S-OZR, relative to LZR, at 11 and 18 weeks of age, and was reduced with training. One hour/day exercise training normalized hindlimb vascular resistance and glucose uptake in 11-week-old OZR, but only moderately improves these vascular and metabolic variables in 18-week-old hyperglycemic animals. Prolonged (12 weeks) training reduced the severity of fasting hyperglycemia in older animals, but at the expense of an increased fasting insulin concentration.

Adaptation, Physiological↗

Effect of pretreatment with ICRF-187 on the total cumulative dose of doxorubicin tolerated by beagle dogs.

Studies were made of the influence of ICRF-187 on the functional and morphological effects of very large cumulative doses of doxorubicin given over a prolonged period of time. Adult beagles of either sex (6.2-11.6 kg) were given doxorubicin (1.75 mg/kg i.v.) either alone or 15 min after ICRF-187 (25 mg/kg, i.v.) at 3-week intervals. Control dogs received ICRF-187 (25 mg/kg, i.v.) or 0.9% saline without doxorubicin. Of eight animals receiving doxorubicin alone, five died; two after a total dose of 12.25 mg/kg and three after 14 mg/kg; three others were in poor condition at the time of euthanasia after 14 mg/kg. Of eight animals receiving both ICRF-187 and doxorubicin, four died; two after 35 mg/kg, one after 43.75 mg/kg, and one after 52.5 mg/kg; two other dogs were euthanized after 43.75 mg/kg because of difficulties encountered in giving i.v. injections, and two dogs survived a total dose of 52.5 mg/kg. All control dogs survived. None of the treatment or control groups developed consistent echocardiographic changes or alterations in mean arterial pressure. By 300 days after onset of treatment, dogs given ICRF-187 and doxorubicin developed significant prolongation of the PQ interval; by 550 days, surviving dogs in this group developed ventricular premature contractions. Each animal receiving doxorubicin alone had severe myocardial lesions (lesion score 3+). Of the animals given ICRF-187 and doxorubicin, one that received 35 mg/kg doxorubicin had no lesions; of four given 43.75 mg/kg, three had no lesions and one had minimal lesions (lesion score 1+); of three given 52.5 mg/kg, one had minimal (lesion score 1+), and two had moderate (lesion score 2+) lesions. Control animals had no myocardial lesions. Thus, ICRF-187 provided significant protection when administered with doxorubicin over a period of 90 weeks, and made it possible to give doses of doxorubicin which otherwise would have been lethal.

Animals↗

Noninvasive measurement of systemic arterial blood pressure in the conscious beagle dog.

The objectives of this study were to evaluate a technique for routine, noninvasive measurement of systemic arterial blood pressure and heart rate (HR) in conscious Beagle dogs for toxicologic research. HR, systolic, diastolic, and mean arterial (MAP) pressures were measured with a DINAMAP research monitor (Model 1255, Critikon, Inc.) as follows: Dogs were restrained in a Harvard dog sling, a neonatal cuff was wrapped around the base of the tail, and blood pressure and HR were determined once a minute. Initially, normal values were obtained, 5-10 trials/session, one to three sessions/day for 15 days in six dogs. The day to day, session to session, and trial variabilities were determined and found to be minimal. The day to day diastolic pressure ranged from 74 +/- 18 to 91 +/- 13 mm Hg, systolic pressure from 125 +/- 25 to 156 +/- 22 mm Hg, MAP from 94 +/- 20 to 113 +/- 15 mm Hg, and HR from 111 +/- 21 to 126 +/- 24 beats/minute (bpm). The effects of various drugs on these parameters were determined. Norepinephrine increased diastolic, systolic, and MAP by 75 to 110 mm Hg and decreased HR by half. Epinephrine increased HR by 20 bpm. Phentolamine decreased diastolic, systolic, and MAP by up to 25 mm Hg. Isoproterenol increased HR by up to 130 bpm and decreased diastolic, systolic, and MAP by 20 mm Hg. In addition, the effect of a classic drug interaction on these parameters was determined. When dogs pretreated with the monoamine oxidase inhibitor tranylcypromine were challenged with tyramine, diastolic, systolic, and MAP pressures were increased, whereas HR was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A model for regional blood flow measurements during cardiopulmonary resuscitation in a swine model.

Recent reports examining regional blood flow during cardiopulmonary resuscitation (CPR) have been criticized for several reasons: (1) cardiac arrest times of 5 min or less are not reflective of the prehospital setting, (2) anesthetic agents may significantly influence autonomic control of regional blood flow, (3) canine cardiac anatomy and coronary blood supply are not reflective of humans and (4) precise validation data for blood flow measurements have not been reported. This study presents a methodology and model for measuring regional blood flow during CPR after a prolonged cardiac arrest. Fifteen swine weighing 15-25.4 kg were instrumented for regional blood flow measurements using tracer microspheres. Regional cerebral and myocardial blood flow were measured during normal sinus rhythm (NSR) and during CPR following a 10-min cardiopulmonary arrest. Regional blood flow (ml/min/100 g) to the cerebral cortices averaged less than 3% of baseline flow (NSR: right cortex = 41.2 +/- 13.8; left cortex = 41.2 +/- 12.2; CPR: right cortex = 1.3 +/- 1.2; left cortex = 1.3 +/- 1.3). Total myocardial blood flow averaged less than 5% of baseline flow (NSR = 211.5 +/- 104.9; CPR = 9.5 +/- 14.9). The flow data demonstrates minimal cardiac and cerebral perfusion with standard CPR following a 10-min arrest. The variability in the pilot data may be used in determining sample sizes for future studies.

Animals↗

Myocardial oxygen delivery/consumption during cardiopulmonary resuscitation: a comparison of epinephrine and phenylephrine.

Our study compared the effect of high-dose epinephrine with the pure alpha-agonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MDO2), myocardial oxygen consumption (MVO2), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MDO2, and MVO2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MDO2, and MVO2 were measured during CPR. Following three minutes of CPR, animals (N = 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO2, and MVO2 were repeated after drug administration. Extraction ratios, defined as MVO2/MDO2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 3 1/2 minutes after drug administration. There was no significant difference in MBF, MDO2, MVO2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +/- 49.4 mL/min/100 g for the group receiving epinephrine 0.2 mg/kg; 7.0 +/- 7.1 mL/min/100 g for the group receiving phenylephrine 0.1 mg/kg; and 36.7 +/- 21.1 mL/min/100 g for the group receiving phenylephrine 1.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of standard doses of epinephrine on myocardial oxygen delivery and utilization during cardiopulmonary resuscitation.

This preliminary study was conducted to evaluate the effects of 0.02 mg/kg of epinephrine (E) on myocardial blood flow (MBF), myocardial oxygen consumption (MVO2), and delivery (MDO2) when administered during CPR after 10-min cardiopulmonary arrest. Five miniature swine were instrumented for MBF measurements using tracer microspheres. Ventricular fibrillation was induced. After 10 min, CPR was begun with a pneumatic compressor. Measurements of MBF, arterial, and coronary sinus blood gases were made. After 3 min of CPR, each animal received 0.02 mg/kg of E. The measurements were repeated and defibrillation was attempted. During CPR, MDO2 and MVO2 were 0.2 +/- 0.3 and 0.2 +/- 0.3 ml/min/100 g tissue, respectively. The myocardial oxygen extraction ratio (ER) was 94.2 +/- 3.0%. After 0.02 mg/kg of E, MDO2 was 1.1 +/- 1.4, MVO2 was 1.0 +/- 1.3, and ER was 93.9 +/- 0.7% (p greater than .05). There were no successful defibrillations. These data indicate that MDO2 improves slightly during CPR after 0.02 mg/kg of E, but it does not meet the oxygen demands of the fibrillating heart.

Animals↗

Pretreatment with ICRF-187 allows a marked increase in the total cumulative dose of doxorubicin tolerated by beagle dogs.

To study the influence of ICRF-187 on the functional and morphological effects of very large cumulative doses of doxorubicin, adult beagle dogs were given doxorubicin (1.75 mg/kg i.v.) either alone or 15 min after ICRF-187 (25 mg/kg, i.v.) at 3-week intervals. Control dogs received ICRF-187 (25 mg/kg, i.v.) or 0.9% saline without doxorubicin. Of eight animals receiving doxorubicin alone, two died after a total dose of 12.25 mg/kg and three died after 14 mg/kg; three others were in poor condition at the time of euthanasia after 14 mg/kg. Of eight animals receiving both ICRF-187 and doxorubicin, one died after 35 mg/kg, two died after 43.75 mg/kg and one died after 52.5 mg/kg; two dogs were euthanatized after 43.75 mg/kg because of difficulties encountered in giving i.v. injections, and two dogs survived a total dose of 52.5 mg/kg. All control dogs survived. None of the treatment or control groups developed consistent echocardiographic changes or alterations in mean arterial pressure. Dogs given ICRF-187 and doxorubicin developed PQ interval prolongation after 300 days and ventricular premature beats after 500 days. Each animal receiving doxorubicin alone had severe myocardial lesions (lesion score 3+). Of the animals given ICRF-187 and doxorubicin, one that received 35 mg/kg doxorubicin had no lesions; of four given 43.75 mg/kg, three had no lesions and one had minimal lesions (lesion score 1+); of three given 52.5 mg/kg, one had minimal (lesion score 1+) and two had moderate (lesion score 2+) lesions. Control animals had no myocardial lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of epinephrine versus methoxamine on regional myocardial blood flow and defibrillation rates following a prolonged cardiorespiratory arrest in a swine model.

Recent studies in swine have shown that larger doses of epinephrine than those currently employed for cardiopulmonary resuscitation (CPR) significantly improve regional myocardial blood flow following prolonged cardiac arrest. The dose-response effect of a pure alpha-adrenergic agonist, methoxamine, on regional myocardial blood flow has not been investigated in this setting. This study compared the effect of high-dose epinephrine with graded doses of methoxamine on regional myocardial blood flow, oxygen delivery/utilization, and defibrillation rates during CPR. Twenty swine were instrumented for regional myocardial blood flow measurements using radiolabeled tracer microspheres. Measurements of regional myocardial blood flow, oxygen delivery, and oxygen consumption were made during normal sinus rhythm. Ventricular fibrillation was then induced. Following 10 minutes of ventricular fibrillation, CPR was initiated with a pneumatic compressor. Regional myocardial blood flow, oxygen delivery, and oxygen consumption were then measured during CPR. Following 3 minutes of CPR, the swine were allocated to one of four treatment groups (five per group): group I, epinephrine 0.2 mg/kg; group II, methoxamine 0.1 mg/kg; group III, methoxamine 1.0 mg/kg; and group IV, methoxamine 10.0 mg/kg. One minute after drug administration, regional myocardial blood flow, oxygen delivery, and oxygen consumption measurements again were made. Three and one half minutes after drug administration, defibrillation was attempted. Regional myocardial blood flow following drug administration was compared using an analysis of covariance. Epinephrine (0.2 mg/kg) significantly improved myocardial blood flow (P less than .002) for all tissues examined compared with all doses of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of high-dose phenylephrine versus epinephrine on regional cerebral blood flow during CPR.

Prior studies have not found the alpha agonist phenylephrine, in a dose of 0.1 mg/kg, to be as effective as 0.20 mg/kg of epinephrine in improving regional cerebral blood flow (CBF) during CPR in swine. We undertook this study to assess whether higher doses of phenylephrine might improve regional CBF. Fifteen swine were allocated to receive either epinephrine 0.2 mg/kg, phenylephrine 1.0 mg/kg, or phenylephrine 10 mg/kg. Regional CBF measurements were made during normal sinus rhythm, during CPR, and during CPR following drug administration. Epinephrine 0.2 mg/kg was significantly better in improving regional CBF to the left and right cerebral cortices, cerebellum, midbrain, and cervical cord than was phenylephrine 1.0 mg/kg. There was no significant difference in regional CBF between the animals receiving epinephrine 0.2 mg/kg and phenylephrine 10 mg/kg. The study shows that large doses of epinephrine and phenylephrine may be required during CPR to improve regional cerebral blood flow following a prolonged arrest.

Animals↗

Alterations in regional blood flow during positive end-expiratory pressure ventilation.

PEEP improves the gas-exchange abnormalities that accompany adult respiratory distress syndrome (ARDS). However, since PEEP decreases cardiac output, it may also alter regional blood flow and therefore, substrate delivery to specific organs. To test this hypothesis, radiolabeled 15-mu microspheres were used to directly quantify the effects of mechanical ventilation with PEEP on regional blood flow to individual organs in animals. Mechanical ventilation alone produced a -21.2 +/- 3.6% and a -28.1 +/- 5.2% decrease in cardiac output at 30 and 60 min, respectively. The addition of 14 cm H2O PEEP resulted in little further reduction in cardiac output at 30 and 60 min (-28 +/- 2.3% and -36.4 +/- 4.9%, respectively). However, 25 cm H2O PEEP reduced markedly (p less than .01) cardiac output (-59.2 +/- 6.1% at 30 min and -55.1 +/- 4.0% at 60 min). Although blood flows to the kidney and brain were maintained, decreases in cardiac output were invariably accompanied by proportional decreases in blood flow to the heart. Intravascular volume expansion with saline (20 ml/kg) during 14 cm H2O PEEP significantly improved cardiac output (3.23 +/- 0.34 to 4.22 +/- 0.13 L/min; p less than .01) and proportionately increased blood flow to several regional vascular beds, including the heart. These data suggest that PEEP decreases cardiac output to produce reversible alterations in blood flow to a number of regional vascular beds. These PEEP-induced alterations in regional blood flow may have important implications for the development of multiple-organ failure in ARDS patients.

Animals↗

Methoxamine versus epinephrine on regional cerebral blood flow during cardiopulmonary resuscitation.

The improvement in cerebral blood flow (CBF) during CPR after epinephrine administration has been attributed to epinephrine's alpha-adrenergic properties. Methoxamine, a pure alpha-1 agonist, has only been shown to be comparable to epinephrine in restoring circulation after cardiac arrest in a canine model. This study compares the effectiveness of equipotent doses of epinephrine and methoxamine in improving CBF during CPR after a prolonged cardiac arrest in a swine model. Twenty-five swine, weighing 15.9 to 28.2 kg, underwent instrumentation for regional CBF using tracer microspheres. CBF was determined during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun with a pneumatic compressor. CBF measurements were again made during CPR. After 3 min of CPR, the swine were randomized to receive 0.02 or 0.2 mg/kg epinephrine, 0.1, 1.0, or 10.0 mg/kg methoxamine. Five swine were allocated to each group. CBF measurements were determined after drug administration and compared using a Bonferroni multiple comparison procedure. A p-value less than .05 was considered statistically significant. This study demonstrated that, after a 10-min cardiac arrest, CBF was extremely low, averaging less than 7 ml/min X 100 g during external CPR. There were no clinically significant improvements in regional CBF after 0.02 mg/kg of epinephrine, or the two lowest doses of methoxamine. The addition of 10 mg/kg of methoxamine clinically improved blood flow only to the most caudal CNS structures, including the pons, medulla, and cervical spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗