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Biomedical subjects

J D Coffman

Publications and source records attributed to J D Coffman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Serotonergic vasoconstriction in human fingers during reflex sympathetic response to cooling.

The effect on finger blood flow (FBF) of 5-hydroxytryptamine (5-HT) in a 25 degrees C room and the S2-serotonergic receptor antagonist, ketanserin, during reflex sympathetic vasoconstriction was studied in normal subjects. Total FBF was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a fingertip injection. 5-HT in doses of 4 and 8 micrograms/min, given by constant infusion via a brachial artery catheter, significantly decreased FBF [32 +/- (SE) 10.4 to 12.8 +/- 6.6 for 4 micrograms/min and to 5.4 +/- 2.6 ml.min-1.100 ml-1 for 8 micrograms/min, P less than 0.05]. Ketanserin (50 micrograms/min) blocked the vasoconstriction caused by 5-HT. During reflex sympathetic vasoconstriction produced by body cooling, ketanserin increased FBF from 4.1 +/- 1.1 to 39.9 +/- 12.9 ml.min-1.100 ml-1 (P less than 0.025). The vasodilation caused by ketanserin was specific for serotonergic receptors, since it occurred during alpha 1-adrenoceptor blockade with prazosin. Furthermore, the decreases in FBF induced by clonidine and angiotensin II were not significantly different before and during ketanserin infusion. Also, ketanserin further increased FBF after vasodilation of reflexly vasoconstricted fingers by the alpha 2-adrenoceptor antagonist, yohimbine, and phentolamine increased FBF during ketanserin infusions. FCF decreased during 5-HT and increased during ketanserin infusions, demonstrating that both capillary and arteriovenous shunt flow were affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Alpha-adrenergic and serotonergic mechanisms in the human digit.

The effects of intra-arterial administration of alpha 1- and alpha 2-adrenoceptor and S2-serotonergic agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction caused by body cooling in normal subjects. Total finger blood flow (FBF) was measured by venous occlusion plethysmography and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra-arterial phenylephrine and clonidine produced dose-related decreases in FBF and increases in finger vascular resistance (FVR); clonidine was the more potent vasoconstrictor. Prazosin effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine and yet caused no significant change in FBF and FVR during reflex sympathetic vasoconstriction. Yohimbine blocked the effect of clonidine but not phenylephrine and caused a significant increase in FBF and decrease in FVR during vasoconstriction. No significant changes occurred in FCF with prazosin or yohimbine. 5-Hydroxytryptamine decreased FBF and increased FVR. The S2-serotonergic antagonist, ketanserin, blocked the effects of 5-hydroxytryptamine. Ketanserin, in the presence of prazosin, significantly increased FBF and decreased FVR in the reflex vasoconstricted subjects. These studies suggest that both alpha 1- and alpha 2-adrenoceptors are present in the digital vascular bed and that sympathetic nerves control the flow through arteriovenous anastomoses primarily by alpha 2-adrenoceptors. S2-serotonergic receptors are also present in the digital vasculature and may be another important mechanism mediating digital vasoconstriction.

Adult↗
PubMed1988

Pathophysiology of obstructive arterial disease.

Intermittent claudication is due to ischemia of working muscles in patients with stenoses or obstructions of large or medium sized arteries. Arteriosclerosis obliterans is by far the most common etiology. As an arterial stenosis develops, the distal blood flow and blood pressure are not affected until a critical diameter occurs. Then, blood flow and blood pressure fall precipitously with further narrowing of the lumen area. The most important factors that influence blood flow and the blood pressure drop across a stenosis are the radius of the stenosis and of the artery, and the velocity of blood flow. The velocity of blood flow varies inversely with the peripheral resistance. A decrease in peripheral resistance which occurs with exercise, vasodilator drugs, or sympathectomy leads to an increased blood flow velocity and an increased pressure drop across a stenosis. Thus, a non-critical stenosis at rest can become critical and limit blood flow during exercise. In arterial occlusions and critical arterial stenoses, the distal perfusion pressure is decreased due to the high resistance of the small collateral vessels but blood flow may be normal at rest. With exercise, the distal perfusion pressure decreases to a lower level due to the fall in peripheral resistance. Then, the external pressure of muscle contraction may close the arterial bed and stop blood flow. The stimulus to collateral blood vessel development is not known but may involve the pressure differential across the involved vascular bed and metabolic products produced during the ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗
PubMed1987

Intra-arterial vasodilator agents to reverse human finger vasoconstriction.

Persistent vasospasm of the digits is difficult to attenuate or reverse. We studied the effect of intra-arterial nitroprusside on humoral and neurogenic digital vasoconstriction. Fingertip blood flow (FBF) was measured by venous occlusion plethysmography and capillary flow (CF) by the disappearance rate of a local injection of radioisotope. Small doses of nitroprusside (1 to 2 micrograms/min) increased FBF in fingers vasoconstricted by intra-arterial norepinephrine (4.7 +/- SE 1.7 to 38.4 +/- 26 ml min-1 100 ml-1 of tissue). Large doses of nitroprusside (up to 40 micrograms/min) did not increase FBF (11.8 +/- 6.0 ml to 6.6 +/- 3.9 ml) in fingers vasoconstricted by sympathetic nerve stimulation (body cooling). Forearm blood flow was measured in six subjects in the cool room and all showed an increase in flow with nitroprusside (6.7 +/- 1.1 ml to 26.0 +/- 6.0 ml), demonstrating that effective doses were used. Nitroglycerin (2.5 to 5 micrograms/min) significantly increased FBF from 5.1 +/- 1.9 ml to 14.8 +/- 6.9 ml as did phentolamine (50 to 100 micrograms/min) from 6.7 +/- 2.8 ml to 36.0 +/- 11.3 ml in sympathetically vasoconstricted subjects. Only phentolamine increased CF significantly (0.8 +/- 0.2 ml to 2.8 +/- 0.6 ml). Nitroprusside is an effective vasodilator for humorally induced vasoconstriction, but sympathetic digital vasoconstriction is resistant to nitroprusside and nitroglycerin is less effective than phentolamine. Phentolamine is the preferred agent because it increased FBF and CF.

Female↗
PubMed1987

Cholinergic vasodilator mechanism in human fingers.

The effect of a cholinergic agonist and antagonist on finger blood flow (FBF) was studied in 10 normal subjects. Total finger blood flow was measured by venous occlusion, air plethysmography, and capillary blood flow (FCF) by the disappearance rate of a radioisotope from a fingertip injection. Methacholine in doses of 10-80 micrograms/min was given by constant infusion via a brachial artery catheter. Average FBF (7.4 +/- 2.5 to 10.9 +/- 4.3 ml X min-1 X 100 ml tissue-1) and vascular resistance (22.4 +/- 4.7 to 21.3 +/- 7.0 mmHg X ml-1 X min X 100 ml tissue) were not significantly affected. However, the half time (t1/2) of the disappearance rate decreased from 50.8 +/- 13.4 to 11.1 +/- 1.5 min (P less than 0.01); a decrease occurred in all subjects. In seven subjects, atropine (0.2 mg) had no affect alone but inhibited the effect of methacholine on FCF (t1/2 47.6 +/- 6.2 to 50.2 +/- 6.7 min) and prevented the redness and sweating of the forearm and hand that occurs with this agent. This study demonstrates a muscarinic cholinergic vasodilator mechanism in the fingertip that uniquely increases capillary blood flow.

Adult↗
PubMed1985

The contribution of the renin-angiotensin system to limb vasoregulation in patients with heart failure: observations during orthostasis and alpha-adrenergic blockade.

1. In patients with congestive heart failure, both the sympathetic nervous system and renin-angiotensin system are often stimulated. In order to assess the contribution of the renin-angiotensin system to limb vascular resistance, the forearm haemodynamic response to captopril was studied in 13 patients with heart failure. 2. Seven subjects were studied while supine and during 60 degrees head-up tilt. To eliminate alpha-adrenergic effects, six additional patients with heart failure were pretreated with intra-arterial phentolamine and then given captopril. Venous occlusion plethysmography was used to determine forearm blood flow and forearm vascular resistance. 3. Tilt did not significantly increase pretreatment plasma renin activity or plasma noradrenaline concentration, nor did it decrease forearm blood flow. Furthermore, captopril did not alter forearm vascular resistance during supine or upright posture. During the phentolamine infusion, however, captopril reduced forearm vascular resistance by 19% (P < 0.05). 4. Despite increased plasma renin activity, captopril did not cause forearm vasodilatation during supine or upright posture in these patients with heart failure. When the contribution of the sympathetic nervous system was eliminated, captopril decreased forearm vascular resistance. Therefore, in patients with congestive heart failure, the sympathetic nervous system is important in limb vasoregulation, and the contribution of the renin-angiotensin system is apparent only after alpha-adrenergic blockade.

Adrenergic alpha-Antagonists↗
PubMed1985

Evaluation of the patient with Raynaud's phenomenon.

Idiopathic Raynaud's phenomenon (Raynaud's disease) is very common among young women. A thorough history and physical examination are the keys to determining the extent of a diagnostic workup. In an otherwise normal and asymptomatic young woman with vasospastic attacks involving symmetric aspects of the digits, a CBC, urinalysis, chest film, and ESR are recommended as a cost-effective workup. If these studies are negative, the disease is probably benign. A history or physical findings consistent with collagen vascular disease, obstructive arterial disease, or carpal tunnel or thoracic outlet syndrome should lead to selected diagnostic tests. Men, persons with onset of vasospastic attacks after age 40, and those with severe disease or trophic changes of the digits deserve a more comprehensive workup to screen for underlying causes.

Adult↗
PubMed1985

Effects of beta-adrenoreceptor-blocking drugs in patients with Raynaud's phenomenon.

Digital vasospastic phenomena have been reported to result from use of nonselective and cardioselective beta-adrenoreceptor-blocking drugs. The effects of 80 mg/day propranolol and 100 mg/day metoprolol on finger hemodynamics and clinical responses were compared with those of placebo in 16 patients with Raynaud's phenomenon. A double-blind, 2 week crossover study design was used with a 2 week washout placebo period between drugs. Total fingertip blood flow (FBF) as determined by venous occlusion plethysmography, fingertip capillary flow (FCF) as determined by radioisotope disappearance rate, and finger systolic blood pressure (FSP) were measured in a 28.3 degrees and a 20 degrees C room at the end of each period. Subjects kept diaries to record vasospastic attacks. There were no significant changes in FBF, FCF, or FSP in the warm or cool environment during drug treatment as compared with during the placebo period. A decrease in pulse rate occurred with both drugs and there was a decrease in blood pressure with metoprolol. There were no significant changes in the number of vasospastic attacks or in the patients' overall evaluation of their conditions while they were receiving the drugs. It is concluded that the presence of Raynaud's phenomenon is not a contraindication to the use of beta-adrenoreceptor-blocking drugs in the normotensive population.

Adrenergic beta-Antagonists↗
PubMed1985

Beta adrenergic-mediated vasodilator response to insulin in the human forearm.

Insulin, in doses sufficient to cause systemic hypoglycemia, decreases vascular resistance; however, a vasoactive effect of insulin in humans, in the absence of hypoglycemia, is unknown. Venous occlusion strain gauge plethysmography was utilized to determine forearm blood flow (FBF) and forearm vascular resistance (FVR) during incremental intra-arterial infusion of insulin (0.1, 0.5 and 1.0 mU/kg/min) in seven normal subjects. With the increasing doses of insulin, FBF increased 55, 76 and 145% and FVR decreased 30, 42 and 58%, respectively. Systemic glucose concentration decreased only during the highest dose insulin infusion. In eight subjects who received insulin during euglycemic glucose clamping, FVR also decreased. Therefore, it was demonstrated that insulin dilates the forearm vasculature in the absence of hypoglycemia. In order to determine whether the vasodilatory effect of insulin was mediated by the sympathetic nervous system, plasma levels of epinephrine and norepinephrine were measured. During the incremental insulin infusions, norepinephrine levels did not change, but epinephrine concentration increased during the 1.0 mU/kg/min infusion when hypoglycemia developed. Furthermore, 21 subjects were pretreated with intra-arterial phentolamine, propranolol or the combination of phentolamine and propranolol. Phentolamine did not potentiate the fall in FVR during insulin administration; however, propranolol attenuated or completely inhibited the changes in FBF and FVR. During combined alpha and beta adrenergic blockade, insulin increased FBF and decreased FVR only during the higher dose insulin infusions. It is concluded that insulin causes forearm vasodilation primarily via a beta adrenergic mechanism. In addition, at the higher doses used in this study, insulin may decrease FVR directly or by a mechanism other than adrenergic stimulation.

Adult↗
PubMed1984

Nifedipine-induced fingertip vasodilation in patients with Raynaud's phenomenon.

The effect of nifedipine on fingertip hemodynamics was studied in 10 patients with Raynaud's phenomenon. Fingertip blood flow (FBF) was determined in a 20 degrees C environment by venous occlusion air plethysmography and fingertip vascular resistance (FVR) was calculated from the mean blood pressure and the FBF. Nifedipine, administered as a 10 mg sublingual dose, increased FBF in 8 of the 10 patients. FVR for the 10 patients decreased 40% from 40.7 +/- 10.8 to 24.2 +/- 6.1 U (p less than 0.05). Seven of the 10 patients were followed in a crossover placebo-controlled clinical trial. The frequency and severity of Raynaud's phenomenon was less in all seven patients when taking nifedipine as compared to placebo. Nifedipine-induced fingertip vasodilation may contribute to clinical improvement in some patients with Raynaud's phenomenon.

Adult↗
PubMed1984

Effect of thromboxane synthetase inhibition in Raynaud's phenomenon.

To determine whether thromboxane A2 may be of pathogenetic importance in Raynaud's phenomenon, finger hemodynamic and clinical responses to dazoxiben, a thromboxane synthetase inhibitor, were studied in 25 subjects. Thirteen subjects had idiopathic Raynaud's disease and 12 subjects had secondary Raynaud's disease. A double-blind, 2-week crossover study design was used. Dazoxiben dose was 100 mg four times a day. Total fingertip blood flow (FBF) by venous occlusion plethysmography, fingertip capillary flow (FCF) by radioisotope disappearance rate, and finger systolic blood pressure (FSP) were measured in a 28.3 degree and a 20 degree room at the end of each period. Subjects kept diaries of vasospastic attacks. For the 25 subjects and the two subgroups, dazoxiben did not improve total FBF, FCF, or FSP. Subjects with idiopathic Raynaud's disease had a small decrease in the number of vasospastic attacks and an increase in percentage of attack-free days on dazoxiben, but in an overall evaluation by the subjects in both subgroups, dazoxiben did not improve symptoms. It is concluded that thromboxane is not of pathogenetic importance in Raynaud's phenomenon and that thromboxane synthesis inhibition is not of therapeutic benefit.

Adult↗
PubMed1984

The effect of histamine on the human fingertip circulation.

The effect of intra-arterial histamine on fingertip blood flow (FBF) and vascular resistance (FVR) was studied in normal subjects during reflex sympathetic vascoconstriction induced by body cooling and vasoconstriction caused by intra-arterial noradrenaline. In a room at 20 degrees C, FBF increased from 15.3 +/- 35.5 (SD) to 28.3 +/- 55.9 ml min-1 100 ml-1 of tissue and FVR decreased from 23.7 +/- 17.7 to 11.9 +/- 9.9 mmHg X ml min-1 100 ml-1 (P less than 0.01) during infusions of histamine (0.5-4 micrograms/min) in 14 subjects. In nine of these subjects, the disappearance half times of local injections of Na131I were measured and decreased from 19.8 +/- 10.9 to 12.9 +/- 7.3 min during histamine infusions, indicating an increase in nutritional flow. Arteriovenous shunt flow was also probably affected, for increases in FBF were sometimes large and FBF increased without a change in the radioisotope half time in two subjects. Neither cimetidine nor pyrilamine (mepyramine) consistently prevented the FBF responses to histamine. Administration of both antihistamines together attenuated the response. During noradrenaline infusions in four subjects, a large increase in FBF (8.9 +/- 10.9 to 39.0 +/- 8.2 ml, P less than 0.005) occurred at the smallest dose (0.5 micrograms/min) of histamine. It is concluded that histamine can vasodilate fingertips and increase nutritional blood flow during reflex sympathetic vasoconstriction. This vasodilatation may be mediated via both histamine H1 and H2 receptors.

Cimetidine↗
PubMed1984

Effect of renin-angiotensin system on limb circulation in normal subjects.

It is not known whether the renin-angiotensin-aldosterone (RAA) system contributes to the regulation of the limb circulation in normal human beings. Accordingly, the effect of the angiotensin converting-enzyme inhibitor, captopril, on forearm vascular resistance (FVR) and forearm venous volume (FVV) was studied in nine normal subjects during states of both sodium loading and sodium depletion. All subjects were studied in the supine position and during 60 degrees head-up tilt. By analysis of variance, the combined intervention of sodium depletion and converting-enzyme inhibition was responsible for a decrease in both FVR and mean blood pressure (BP). In sodium-depleted subjects, converting-enzyme inhibition decreased supine mean BP 7.0% and supine FVR 22.8% but did not change FVV. Neither the fall in BP nor the fall in FVR, however, was significantly augmented by tilting from a supine to upright posture. In sodium-loaded subjects, captopril did not alter BP, FVR, or FVV in recumbent or upright positions. Therefore, the RAA system contributes to the maintenance of blood pressure and limb vascular resistance only in sodium-depleted subjects. Limb venous capacitance in normal subjects is not regulated by the RAA system.

Adult↗
PubMed1983

The peripheral circulation and treatment of hyperlipoproteinemias.

Forty patients with hyperlipoproteinemia were followed 4-9.3 years by non-invasive tests of their lower extremity circulation. Twenty-eight patients were treated by diet and/or drugs, and 12 patients were controls. Although all patients had abnormal non-invasive tests, only 15 patients had intermittent claudication. Seven patients had improved circulation tests while 13 showed a deterioration in the tests; 20 patients had no changes. The patients who showed improvement in tests had the highest incidence of intermittent claudication and the lowest average ankle to brachial artery systolic blood pressure index. Although treatment patients had a significant decrease in total cholesterol, triglycerides, and VLDL, no significant differences were found when the results of the circulation tests were analyzed according to treatment or control status of the patients, to abnormal lipid patterns, or, ignoring treatment status, to a decrease in lipids. The patients who showed a deterioration in tests had a significantly higher total cholesterol level at the beginning of, but not during, the study and did not significantly decrease their triglycerides. No significant changes occurred in HDL, LDL, or VLDL. This study presents a methodology for the long-term, non-invasive assessment of peripheral arterial disease and a pilot study for its application. Despite the small number of patients studied, the failure to demonstrate benefit would discourage a larger clinical trial of this treatment protocol.

Adult↗
PubMed1983

Digital vasodilatation during mental stress in patients with Raynaud's disease.

Fingertip blood flow was measured by venous occlusion plethysmography before and during a stressful mental task consisting of rapid serial arithmetic calculations in a 25 degrees C room. Significant rises in heart rate and blood pressure indicated that stress was actually induced in all individuals. During mental stress in normal subjects, blood flow decreased (46.4 +/- 6.2 to 22.4 +/- 4.9 ml X min-1 per 100 ml tissue; P less than 0.01) and vascular resistance increased (2.1 +/- 0.4 to 7.6 +/- 2.2 units; P less than 0.01). Patients with Raynaud's disease unexpectedly increased blood flow (15.4 +/- 4.2 to 21.6 +/- 5.7; P = 0.05) and decreased vascular resistance (9.7 +/- 2.3 to 7.1 +/- 1.4; P = 0.05). Ten additional normal subjects were studied in a cool room (20 degrees C). Their digits remained vasoconstricted during stress, as blood flow (7.4 +/- 2.9 to 5.1 +/- 1.3) and vascular resistance (31.5 +/- 11.1 to 34.4 +/- 8.2) varied insignificantly (P greater than 0.10). The digital vasodilatation which occurs during mental stress in patients with Raynaud's disease was not altered by pretreatment with oral indomethacin, with intra-arterial propranolol or atropine, or by digital nerve block. These findings suggest the existence of an active digital vasodilatory mechanism in patients with Raynaud's disease.

Adult↗
PubMed1983

Principles of conservative treatment of occlusive arterial disease.

Conservative medical treatment is indicated for patients who have stable symptoms of intermittent claudication without rest symptoms or signs, rapidly progressive disease, or disability interfering with gainful employment (see Fig. 1). Valuable general measures include meticulous care of the limbs, avoidance of trauma and infections, and maintenance of normal body weight. Cessation of tobacco smoking is extremely important, and a regimented exercise program is therapeutically beneficial (see Table 1). The high risk factors of diabetes mellitus and hypertension should be controlled. Hyperlipoproteinemia should be treated if present, but it is currently not known if treatment of elevated cholesterol or triglyceride levels prevents progression of or reverses the disease process. If a recent arterial occlusion is suspected, fibrinolytic therapy can be expected to benefit approximately one third of the patients. Anticoagulants and vasodilator drugs have not been shown to be of value. In patients with rest symptoms or signs, who are not candidates for surgical revascularization of the limb, bed rest with dependency of the limb in a warm environment, good foot care, and analgesics are most important. Ulcers should be treated with wet dressings to preserve granulation tissue, and parenteral antibiotics are used if infection is present. When rest symptoms or trophic lesions have disappeared or improved, the patient may be gradually ambulated but should continue to sleep with the head of the bed elevated and should maintain meticulous foot care.

Animals↗