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Biomedical subjects

J R Michael

Publications and source records attributed to J R Michael.

At least 73 records · Page 4Linked to original sources
PubMed1987

Pharmacologic therapy of cor pulmonale.

Oxygen remains the mainstay for the therapy of pulmonary hypertension and right ventricular failure in patients with COPD. Oxygen selectively vasodilates the pulmonary vascular bed, increases oxygen delivery and mixed venous oxygen tension, and reduces the elevated pulmonary vascular resistance and right ventricular work. Clinically, oxygen therapy improves neurologic function, exercise performance, and survival. Digitalis therapy is indicated only in patients with biventricular failure or supraventricular tachycardia. Diuretics should be used carefully. Two investigational therapies offer promise, but are unproven. Almitrine increases arterial PO2, and vasodilators lower pulmonary vascular resistance. Despite the proper use of the drugs reviewed in this chapter, the current therapy for the treatment of right ventricular hypertrophy and failure is limited. Improved therapy will require a better understanding of the pathophysiology that causes a hypertrophied ventricle to fail.

Humans↗
PubMed1986

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs.

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60-140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.

Adrenergic alpha-Antagonists↗
PubMed1986

Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation.

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Nitrendipine attenuates the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia in rats.

We designed experiments to determine whether intermittent hypoxia would produce significant pathologic and physiologic changes in rats and whether pretreatment with a calcium channel blocker, nitrendipine, would reduce the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia. Intermittent exposure to hypobaric hypoxia (0.5 atmospheres) 10 h a day for 30 days increased the hematocrit (65 +/- 1 versus 42 +/- 1%, mean +/- SEM), right ventricular systolic pressure (33 +/- 1 versus 20 +/- 1 mmHg), and right ventricular weight adjusted for body weight (RV/BW) (126 +/- 6 versus 60 +/- 2 mg/100 g) in male Sprague-Dawley rats. Intermittent hypoxia also increased the percentage of small pulmonary vessels with muscle (76 +/- 3 versus 19 +/- 5%) and the thickness of the vessel wall as a percentage of the total vessel diameter (34 +/- 1 versus 22 +/- 1%). Nitrendipine (10 mg/kg) prevented the acute increase in right ventricular systolic pressure caused by hypoxia. Chronic treatment with nitrendipine (10 mg/kg given twice a day by gavage for 30 days) significantly reduced the increase in hematocrit (61 +/- 1 versus 65 +/- 1%), right ventricular systolic pressure (29 +/- 1 versus 33 +/- 1 mmHg), and RV/BW (108 +/- 4 versus 126 +/- 6 mg/100 g) caused by hypoxia. Chronic treatment with nitrendipine also reduced the percentage of small pulmonary vessels with muscle (38 +/- 8 versus 76 +/- 3%) and prevented the increase in vessel wall thickness (20 +/- 2 versus 34 +/- 1%). Thus, nitrendipine treatment significantly reduces the right ventricular hypertrophy and pulmonary vascular changes caused by intermittent hypoxia.

Animals↗
PubMed1986

Leukotriene D4 increases pulmonary vascular permeability and pressure by different mechanisms in the rabbit.

We designed experiments to define the effects of leukotriene D4 (LTD4) in the rabbit lung and to determine whether or not these effects were due to the synthesis of cyclooxygenase products. Infusion of LTD4 (0.01, 0.03, and 0.10 microgram) into the rabbit pulmonary vasculature caused a dose-related increase in pulmonary arterial pressure and tracheal pressure. Pretreatment with FPL 55712 (38 microM), a leukotriene receptor antagonist, or indomethacin (10 micrograms/ml of perfusate) completely prevented the increase in tracheal and pulmonary arterial pressure. We also studied the effect of LTD4 on pulmonary vascular permeability by measuring lung weight gain at 4 levels of left atrial pressures (0, 5, 10, and 15 mmHg). Leukotriene D4 increased lung weight gain at all levels of left atrial pressure compared with that in the control group. Pretreatment with FPL 55712 completely inhibited the increase in vascular permeability caused by LTD4. Although pretreatment with indomethacin blocked the increase in tracheal and vascular pressure caused by LTD4, it did not prevent the increase in vascular permeability. We conclude that in the rabbit, LTD4 increases tracheal pressure, pulmonary arterial pressure, and pulmonary vascular permeability. Leukotriene D4 increases tracheal and pulmonary arterial pressure by stimulating the synthesis of cyclooxygenase products, and it increases vascular permeability through a mechanism that does not require the synthesis of cyclooxygenase products.

Animals↗
PubMed1985

Calcium channel blockers in hypoxic pulmonary hypertension.

Hypoxia is the major cause of pulmonary hypertension and right ventricular hypertrophy in chronic obstructive pulmonary disease, cystic fibrosis, kyphoscoliosis, chronic mountain sickness, and the obesity-hypoventilation and sleep apnea syndromes. Pulmonary hypertension develops in these patients because the long-standing vasoconstriction produced by hypoxia causes muscular hypertrophy of the pulmonary arteries and arterioles. These pathologic changes may regress if alveolar hypoxia is corrected and hypoxic pulmonary vasoconstriction is continuously inhibited. Intermittent inhibition of hypoxic pulmonary vasoconstriction does not reverse these pathologic changes. Since patient noncompliance with oxygen therapy makes it difficult to achieve continual relief of alveolar hypoxia, a drug that inhibits hypoxic vasoconstriction may be useful. Experimental findings indicate that hypoxic pulmonary vasoconstriction requires calcium influx and can be inhibited by certain slow-channel calcium blockers. Studies also demonstrate that slow-channel calcium antagonists can attenuate the pulmonary hypertension and right ventricular hypertrophy produced in rats by chronic hypoxia. Recently, two studies have shown that nifedipine inhibits hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease. If further studies demonstrate that these short-term effects are sustained, certain slow-channel calcium blockers may become a useful adjuvant to low-flow oxygen therapy in the treatment of hypoxic pulmonary hypertension.

Animals↗
PubMed1985

Multifocal atrial tachycardia: a toxic effect of theophylline.

Sixteen patients with multifocal atrial tachycardia (MAT) who were taking theophylline were identified over 6 months. After theophylline was discontinued the atrial rate fell and MAT resolved in all sixteen patients. Five patients were challenged with intravenous aminophylline to investigate the role of theophylline in the genesis of MAT. MAT with a rapid ventricular response occurred in all five even though metabolic and respiratory variables did not change. MAT returned on challenge in three patients in whom serum theophylline levels were within the generally accepted therapeutic range (10-20 mg/l). In individual patients, theophylline had a dose-related effect on the atrial rate and the amount of ectopic atrial activity. Thus, theophylline may commonly precipitate MAT and treatment with the drug should be carefully considered in patients with respiratory insufficiency and MAT.

Aged↗
PubMed1985

Beneficial effect of epinephrine infusion on cerebral and myocardial blood flows during CPR.

It is hypothesized that epinephrine improves the ability to resuscitate the heart through a mechanism thought to be related to the increase in aortic pressure. Our results with epinephrine infusion during CPR are consistent with this hypothesis. Epinephrine selectively increased vascular resistance in noncerebral, noncoronary vascular beds, as indicated by a decrease in microsphere-determined blood flow in these areas. This increased vascular resistance raised aortic pressure during the chest compression phase and the relaxation phase of CPR. Because intracranial and right atrial pressures were only slightly higher with epinephrine, cerebral and myocardial perfusion pressures and blood flows were significantly improved. This beneficial effect (compared to no administration of a vasopressor) was more pronounced as CPR progressed beyond ten minutes. Enhanced cerebral and myocardial perfusion occurred with epinephrine when either the conventional or simultaneous compression and ventilation (SCV) mode of CPR was employed in dogs. Similar selective perfusion was sustained for 50 minutes of SCV-CPR with epinephrine, even when the onset of CPR was delayed five minutes. Regional brain blood flow differed in the delayed-CPR group in that cerebellum, brain stem, and thalamic regions initially had higher blood flows. In an infant animal model of CPR using conventional CPR in piglets, epinephrine also was found to increase cerebral and myocardial blood flows. These results show that administration of epinephrine benefits different age groups of different species with different modes of CPR; that benefits occur even with delayed onset of CPR which is associated with additional anoxia and acidosis; and that epinephrine administration is particularly effective in sustaining cerebral and coronary perfusion during prolonged CPR.

Aging↗
PubMed1985

Efficacy and safety of naloxone in septic shock.

We evaluated the effectiveness and safety of iv naloxone in 12 septic patients who remained hypotensive despite volume replacement, appropriate antibiotics, and vasopressor therapy. Only four patients responded positively to naloxone, by increases in mean arterial pressure of between 10 to 15 mm Hg that lasted for 15 to 60 min. These patients could not be distinguished from the others on the basis of underlying illness, laboratory or physical findings, length of preceding hypotension, or glucocorticoid therapy. Four patients had adverse reactions: one developed pulmonary edema, one patient had a grand-mal seizure, and two patients became severely hypotensive. We conclude that in patients with well-established septic shock, naloxone does not reliably improve mean arterial pressure or other physiologic variables, and may cause severe adverse reactions.

Aged↗
PubMed1985

Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs.

To characterize quantitatively the relationships among pulmonary vascular pressures (P) and cardiac output (Q) in conscious dogs, multipoint plots of pulmonary arterial (PAP), pulmonary capillary wedge (PCWP), PAP - PCWP, and left atrial (LAP) pressure versus Q were generated by graded constriction of the thoracic inferior vena cava (IVC) to vary Q. Slopes and extrapolated pressure intercepts from linear regression fits to the P/Q plots were determined for three inspired oxygen tensions: normoxia, hyperoxia, and hypoxia. During normoxia (arterial Po2 87 +/- 1 Torr), the extrapolated pressure intercepts for PAP, PCWP, and PAP - PCWP were virtually 0 mmHg, and for LAP, substantially negative (-5.5 +/- 1.1 mmHg; P less than 0.01). Hyperoxia (Po2 365 +/- 28 Torr) had no effect on any of the P/Q plots. In contrast, hypoxia (Po2 51 +/- 1 Torr) significantly increased the intercepts (P less than 0.01) as well as the slopes (P less than 0.05) of PAP and PAP - PCWP versus Q, but produced only minor changes in PCWP and LAP versus Q. These hypoxia-induced changes in intercepts, perhaps related to changes in critical closing pressures, demonstrate the limitations of pulmonary vascular resistance calculations (quotient of pressure gradient and Q) in quantifying changes in pulmonary vasomotor tone. In this way, the IVC constriction technique provides a more complete description of P/Q relationships than that permitted by simple calculations of pulmonary vascular resistance. We conclude that this technique can be utilized to investigate the effects of other physiological and pharmacological interventions on pulmonary vasomotor tone in conscious dogs.

Animals↗
PubMed1985

Thromboxane-induced pulmonary vasoconstriction: involvement of calcium.

Infusion of tert-butyl hydroperoxide (t-bu-OOH) or arachidonic acid into rabbit pulmonary arteries stimulated thromboxane B2 (TxB2) production and caused pulmonary vasoconstriction. Both phenomena were blocked by cyclooxygenase inhibitors or a thromboxane synthase inhibitor. The increase in pulmonary arterial pressure caused by either t-bu-OOH or arachidonic acid infusion correlated with the concentration of TxB2 in the effluent perfusate. The concentration of TxB2 in the effluent perfusate, however, was always 10-fold greater after arachidonic acid infusion. In the rabbit pulmonary vascular bed lipoxygenase products did not appear involved in the vasoactive response to t-bu-OOH or exogenous arachidonic acid infusion. Calcium entry blockers or a calcium-free perfusate prevented the thromboxane-induced pulmonary vasoconstriction. Calmodulin inhibitors also blocked the pulmonary vasoconstriction induced by t-bu-OOH without affecting the production of TxB2 or prostacyclin. These results suggest that thromboxane causes pulmonary vasoconstriction by increasing cytosol calcium concentration.

Angiotensin II↗
PubMed1985

Mechanism of hyperoxia-induced pulmonary vascular paralysis: effect of antioxidant pretreatment.

We designed experiments using isolated rabbit lungs to determine the effect of hyperoxia on the pulmonary vasoconstriction caused by the infusion of the lipid peroxide tert-butyl hydroperoxide (t-bu-OOH), which produces vasoconstriction by stimulating the pulmonary synthesis of thromboxane. Exposure to 48-60 h of 100% O2 at 1 ATA markedly reduced the increase in pulmonary artery pressure caused by t-bu-OOH infusion. We also investigated whether the mechanism for the attenuated vasoconstriction was due to altered production of arachidonate mediators or oxidant-induced damage to the contractile mechanism. In addition to infusing t-bu-OOH, which selectively stimulates thromboxane production, we also infused Intralipid, an esterified fatty acid emulsion that stimulates production of both thromboxane and prostacyclin. These experiments were done to study the effect of hyperoxia on prostacyclin synthesis. To determine if antioxidant therapy would prevent the changes in mediator production and vascular reactivity caused by hyperoxia, we pretreated animals with the antioxidants butylated hydroxyanisole (BHA) or vitamin E. The lack of vascular reactivity to t-bu-OOH was not due to a decrease in thromboxane synthesis or an increase in prostacyclin synthesis. Hyperoxia did not affect thromboxane synthesis during basal conditions or after stimulation of synthesis by t-bu-OOH. 100% O2 also did not effect the basal synthesis of prostacyclin by the lung. Hyperoxia did, however, markedly reduce prostacyclin synthesis when it was stimulated by Intralipid infusion. Antioxidant pretreatment did not reverse the inhibition of prostacyclin synthesis but did prevent the loss of vascular reactivity caused by hyperoxia. Thus hyperoxia causes vascular paralysis through oxidant-induced injury to the pulmonary vasculature.

Animals↗
PubMed1985

Isoproterenol or aminophylline attenuate pulmonary edema after acid lung injury.

We tested the hypothesis that isoproterenol and aminophylline would reduce both the pulmonary hypertension and increased pulmonary vascular permeability caused by the intratracheal instillation of hydrochloric acid. The lungs of New Zealand white rabbits were studied using a blood-perfused isolated lung preparation. Changes in pulmonary artery pressure and lung weight were measured for 30 min after acid injury (2 ml/kg 0.1 N HCl). In a control group without acid injury, pulmonary artery pressure and lung weight did not change throughout 1 h of perfusion. In an acid control group, pulmonary artery pressure increased 11 +/- 3 mmHg (p less than 0.01), and lung weight increased 19.2 +/- 5.1 g during the 30 min after acid injury (p less than 0.001). Pretreatment with aminophylline (p less than 0.01) or isoproterenol (p less than 0.001) completely prevented the increase in pulmonary artery pressure after acid instillation. Pretreatment with aminophylline strikingly reduced the increase in lung weight caused by acid injury to 3.6 +/- 1.0 g over 30 min (p less than 0.01). Pretreatment with isoproterenol prevented any increase in lung weight (0.5 +/- 0.5 g over 30 min, p less than 0.01). Post-treatment with isoproterenol beginning 3 min after acid instillation also prevented the increase in pulmonary artery pressure (p less than 0.01) and markedly reduced the increase in lung weight to 5.8 +/- 2.4 g over 30 min (p less than 0.01). The beneficial effect of isoproterenol is mediated through activation of beta-adrenergic receptors because propranolol reverses its effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1985

Use of calcium channel blockers in hypoxic lung disease.

COPD patients who are hypoxic develop pulmonary hypertension primarily because alveolar hypoxia induces muscular hypertrophy of pulmonary arteries. This muscular hypertrophy will regress in animals if they receive continuous oxygen therapy. Since many COPD patients refuse to use oxygen continuously, calcium channel blockers, which inhibit hypoxic pulmonary vasoconstriction, may be effective adjuvant therapy. Nifedipine lowers pulmonary vascular resistance during rest and exercise in hypoxic COPD patients.

Calcium Channel Blockers↗
PubMed1985

Cardiopulmonary resuscitation, brain blood flow, and neurologic recovery.

A review of survival rates and neurologic outcome after cardiac resuscitation indicates the importance of rapid initiation of cardiopulmonary resuscitation (CPR) and of finding ways to further improve cerebral blood flow during CPR. Mechanisms for generating blood flow to the brain during CPR and experimental strategies for enhancing cerebral viability are discussed.

Cerebrovascular Circulation↗
PubMed1984

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗