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Biomedical subjects

G Matheis

Publications and source records attributed to G Matheis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting.

BACKGROUND: An alarming incidence (1% to 83%) of neuropsychological dysfunction has been reported after operations using cardiopulmonary bypass (CPB). The present clinical study re-evaluates these complications with current CPB technology in a strictly selected low-risk group of coronary artery bypass (CABG) patients. METHODS: 76 CABG patients, without history of stroke or internal carotid artery stenosis, were examined before, 5 days after, and 2 months after surgery. A neuropsychological test battery was employed according to the "Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac Surgery". Tests include the Block Design Test (problem-solving strategies, recognition and analysis of forms), the Trail Making Test (cognitive achievement at speed), and the Digit Span Test (short-term memory and memory of figures). RESULTS: Both postoperative test scores were not significantly decreased as compared to preoperative values. In contrast, neuron specific enolase (NSE) and S100 b protein, biochemical markers of cerebral injury, increased markedly during and immediately after surgery (NSE preop.: 7.07 +/- 2.40 ng/ml, 1 h postop.: 13.64 +/- 4.50 ng/ml, p < 0.001; S100 b preop.: 0.04 +/- 0.07 ng/ml, after crossclamp: 0.90 +/- 0.69 ng/ml, p < 0.001). One patient displayed postoperative transitional syndrome, another patient suffered from transitory paresis and hypesthesia of the left arm, which disappeared during hospital stay. CONCLUSIONS: Biochemical markers demonstrate significant postoperative cerebral injury during and immediately after CPB. However, CPB for CABG does not lead to marked impairment of neuropsychological scores, and clinically relevant neurological findings were observed in one patient only.

Aged↗
PubMed1997

Heparin-induced thrombocytopenia type II: perioperative management using danaparoid in a coronary artery bypass patient with renal failure.

An 84-year-old patient with heparin-induced thrombocytopenia (HIT), global cardiac decompensation, and acute renal failure underwent a cardiosurgical intervention using an extracorporeal circuit. For systemic anticoagulation danaparoid (Orgaran) was applied as a heparin substitute preoperatively and maintained for systemic anticoagulation during ECC despite it being eliminated by the kidney. The postoperative recovery was prolonged due to bleeding complications. During cardiopulmonary bypass (216 min) the target level of anti-factor Xa was 1.5 UI/ml. This required continuous infusion and an occasional bolus of danaparoid. Coagulation in the extracorporeal circuit was observed twice at plasma levels below 1.4 IU/ml. There were no thromboembolic or neurologic events. We did not retransfuse blood from the extracorporeal circuit or the cardiotomy reservoir after bypass, but because elimination of danaparoid was impaired in this patient and there is no neutraliser available antifactor Xa postoperatively exceeded 0.6 IU/ml for 30 hours. Diffuse bleeding with tamponade resulted. Weaning the patient from the respirator was achieved 12 hours after the last re-exploration. From the 4th postoperative day 750 IU of danaparoid were administered twice daily subcutaneously for thrombosis prevention. On the 6th postoperative day discharge from the ICU was possible. We conclude that the application of danaparoid for cardiopulmonary bypass in patients suffering from acute renal failure may be complicated by hemorrhage.

Acute Kidney Injury↗
PubMed1996

Controlled limb reperfusion in patients having cardiac operations.

HYPOTHESIS: Severe limb ischemia in patients having cardiac operations may occur after intraaortic balloon pump insertion, prolonged femoral vessel cannulation, percutaneous cardiopulmonary bypass, dissecting aneurysms, or emboli. Normal blood reperfusion can cause a postischemic syndrome that increases morbidity and mortality. This clinical study is based on an experimental infrastructure patterned after controlled cardiac reperfusion. (1) It tests the hypothesis that controlled limb reperfusion (i.e., modifying the composition of the initial reperfusate and the conditions of reperfusion) reduces the local and systemic complications seen after normal blood reperfusion. (2) It reports initial clinical application of this strategy in three cardiac surgery centers. METHODS: Controlled limb reperfusion was applied to 19 patients with signs of severe prolonged unilateral or bilateral ischemia (including paralysis, anesthesia, and muscle contracture); six patients (32%) were in cardiogenic shock. The mean ischemic duration was 26 +/- 6 hours. The reperfusion method includes a 30-minute infusion into the distal vessels of a normothermic reperfusate solution mixed with the patient's arterial blood (obtained proximal to the obstruction) in a 6:1 blood/reperfusate ratio. Data are mean +/- standard error of the mean. RESULTS: Sixteen patients (84%) survived with salvaged and functional limbs at the time of discharge. No renal, cardiac, pulmonary, cerebral, or hemodynamic complications developed in the survivors. The three deaths occurred in patients undergoing controlled limb reperfusion while in profound postoperative cardiogenic shock; neither postischemic edema nor contracture developed in any of them. CONCLUSIONS: These findings show that controlled limb reperfusion can be applied readily with standard equipment that is used for cardiac surgery and may salvage limbs while reducing postreperfusion morbidity and mortality.

Adult↗
PubMed1995

Studies of hypoxemic/reoxygenation injury: without aortic clamping. II. Evidence for reoxygenation damage.

This study tested the hypothesis that the developing heart is susceptible to oxygen-mediated damage after reintroduction of molecular oxygen and that this "unintended" reoxygenation injury causes lipid peroxidation and functional depression that may contribute to perioperative cardiac dysfunction. Among 49 Duroc-Yorkshire piglets (2 to 3 weeks old, 3 to 5 kg) 15 control studies were done without hypoxemia to test the effects of the surgical preparation (n = 10) and 60 minutes of cardiopulmonary bypass (n = 5). Twenty-nine piglets underwent up to 2 hours of ventilator hypoxemia (with inspired oxygen fraction reduced to 6% to 7%) to lower arterial oxygen tension to approximately 25 mm Hg. Five piglets did not undergo reoxygenation to determine alterations caused by hypoxemia alone. Twenty-four others received reoxygenation by either raising ventilator inspired oxygen fraction to 1.0 (n = 12) or instituting cardiopulmonary bypass at oxygen tension 400 mm Hg (n = 12). Ventilator hypoxemia produced sufficient hemodynamic compromise and metabolic acidosis that 18 piglets required premature reoxygenation (78 +/- 12 minutes). To avoid the influence of acidosis and hemodynamic deterioration during ventilator hypoxemia, five others underwent 30 minutes of hypoxemia during cardiopulmonary bypass (circuit primed with blood at oxygen tension 25 mm Hg) and 30 minutes of reoxygenation (oxygen tension 400 mm Hg) during cardiopulmonary bypass. Biochemical markers of oxidant damage included measurement of coronary sinus and myocardial conjugated dienes to determine lipid peroxidation and antioxidant reserve capacity assessed by incubating myocardial tissue in the oxidant t-butylhydroperoxide. Functional recovery was determined by inscribing pressure volume loops to determine end-systolic elastance and Starling curves by volume infusion. No biochemical or functional changes occurred in control piglets. Hypoxemia without reoxygenation did not change plasma levels of conjugated dienes, but lowered antioxidant reserve capacity 24%. Reoxygenation by ventilator caused refractory ventricular arrhythmias in two piglets (17% mortality), raised levels of conjugated dienes 45%, and reduced antioxidant reserve capacity 40% with recovery of 39% of mechanical function in the survivors. Comparable biochemical and functional changes occurred in piglets undergoing ventilator hypoxemia and/or cardiopulmonary bypass hypoxemia and reoxygenation on cardiopulmonary bypass. We conclude that hypoxemia increases vulnerability to reoxygenation damage by reducing antioxidant reserve capacity and that reoxygenation by either ventilator or cardiopulmonary bypass produces oxidant damage with resultant functional depression that is not a result of cardiopulmonary bypass. These findings suggest that initiation of cardiopulmonary bypass in cyanotic immature subjects causes an unintended reoxygenation injury, which may increase vulnerability to subsequent ischemia during surgical repair.

Alkadienes↗
PubMed1995

Studies of hypoxemic/reoxygenation injury: without aortic clamping. V. Role of the L-arginine-nitric oxide pathway: the nitric oxide paradox.

This study tests the hypothesis that nitric oxide, which is endothelial-derived relaxing factor, produces reoxygenation injury via the L-arginine-nitric oxide pathway in hypoxemic immature hearts when they are placed on cardiopulmonary bypass. Twenty 3-week-old piglets undergoing 2 hours of hypoxemia (oxygen tension about 25 mm Hg) on a ventilator were reoxygenated by initiating cardiopulmonary bypass (oxygen tension about 400 mm Hg). Five animals were not treated, whereas the pump circuit was primed with the nitric oxide-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) in five piglets. L-Arginine, the substrate for nitric oxide, was administered in a fivefold excess (20 mg/kg), together with L-NAME in five piglets (L-NAME and L-arginine), and given alone in five other piglets (L-arginine). Five normoxemic, instrumented piglets served as a control group, and five others underwent 30 minutes of cardiopulmonary bypass without preceding hypoxemia. Left ventricular contractility was determined as end-systolic elastance by pressure-dimension loops. Myocardial conjugated dienes were measured as a marker of lipid peroxidation, and the antioxidant reserve capacity (malondialdehyde production in tissue incubated with t-butylhydroperoxide) was measured. Nitric oxide level was determined in coronary sinus plasma as its spontaneous oxidation product, nitrite. Cardiopulmonary bypass per se did not alter left ventricular contractility, cause lipid peroxidation, or lower antioxidant capacity. Reoxygenation without treatment depressed cardiac contractility (end-systolic elastance 38% +/- 12% of control*), raised nitric oxide (127% above hypoxemic values), increased conjugated dienes (1.3 +/- 0.2 vs 0.7 +/- 0.1, control*), and reduced antioxidant reserve capacity (910 +/- 59 vs 471 +/- 30, control*). Inhibition of nitric oxide production by L-NAME improved end-systolic elastance to 84% +/- 12%,** limited conjugated diene elution (0.8 +/- 0.1 vs 1.3 +/- 0.2, no treatment**), and improved antioxidant reserve capacity (679 +/- 69 vs 910 +/- 59, no treatment**). Conversely, L-arginine counteracted these beneficial effects of L-NAME, because left ventricular function recovered only 24% +/- 6%,* conjugated dienes were 1.2 +/- 0.1,* and antioxidant reserve capacity was 826 +/- 70.* L-Arginine alone caused the same deleterious biochemical changes as L-NAME/L-arginine and resulted in 60% mortality. The close relationship between postbypass left ventricular dysfunction (percent end-systolic elastance) and myocardial conjugated diene production (r = 0.752) provides in vivo evidence that lipid peroxidation contributes to myocardial dysfunction after reoxygenation.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkadienes↗
PubMed1995

Studies of hypoxemic/reoxygenation injury: without aortic clamping. VIII. Counteraction of oxidant damage by exogenous glutamate and aspartate.

Previous studies show that (1) hypoxemia depletes immature myocardium of amino acid substrates and their replenishment improves ischemic tolerance, (2) reoxygenation on cardiopulmonary bypass causes oxygen-mediated damage without added ischemia, and (3) this damage may be related to the nitric oxide-L-arginine pathway that is affected by amino acid metabolism. This study tests the hypothesis that priming the cardiopulmonary bypass circuit with glutamate and aspartate limits reoxygenation damage. Of 22 immature Duroc-Yorkshire piglets (< 3 weeks old), five were observed over a 5-hour period (control), and five others underwent 30 minutes of CPB without hypoxemia (cardiopulmonary bypass control). Twelve others became hypoxemic by reducing ventilator inspired oxygen fraction to 6% to 7% (oxygen tension about 25 mm Hg) before reoxygenation on cardiopulmonary bypass for 30 minutes. Of these five were untreated (no treatment), and the cardiopulmonary bypass circuit was primed with 5 mmol/L glutamate and aspartate in seven others (treatment). Left ventricular function before and after bypass was measured by inscribing pressure-volume loops (end-systolic elastance). Myocardial conjugated diene levels were measured to detect lipid peroxidation, and antioxidant reserve capacity was tested by incubating cardiac muscle with the oxidant t-butylhydroperoxide to determine the susceptibility to subsequent oxidant injury. CPB (no hypoxemia) allowed complete functional recovery without changing conjugated dienes and antioxidant reserve capacity, whereas reoxygenation injury developed in untreated hearts. This was characterized by reduced contractility (elastance end-systolic recovered only 37% +/- 8%*), increased conjugated diene levels (1.3 +/- 0.1 vs 0.7 +/- 0.1*), and decreased antioxidant reserve capacity (910 +/- 59 vs 471 +/- 30 malondialdehyde nmol/g protein at 2 mmol/L t-butylhydroperoxide*). In contrast, priming the cardiopulmonary bypass circuit with glutamate and aspartate resulted in significantly better left ventricular functional recovery (75% +/- 8% vs 37% +/- 8%*), minimal conjugated diene production (0.8 +/- 0.1 vs 1.3 +/- 0.1*), and improved antioxidant reserve capacity (726 +/- 27 vs 910 +/- 59 malondialdehyde nmol/g protein*) (*p < 0.05 vs cardiopulmonary bypass control). We conclude that reoxygenation of immature hypoxemic piglets by the initiation of cardiopulmonary bypass causes myocardial dysfunction, lipid peroxidation, and reduced tolerance to oxidant stress, which may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). These data suggest that supplementing the prime of cardiopulmonary bypass circuit with glutamate and aspartate may reduce these deleterious consequences of reoxygenation.

Alkadienes↗
PubMed1995

Studies of hypoxemic/reoxygenation injury: with aortic clamping. X. Exogenous antioxidants to avoid nullification of the cardioprotective effects of blood cardioplegia.

This study tests the hypothesis that reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an "unintended" reoxygenation injury that (1) nullifies the cardioprotective effects of blood cardioplegia and (2) is avoidable by adding antioxidants N-(2-mercaptopropionyl)-glycine plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (2 to 3 weeks) underwent 30 minutes of aortic clamping with a blood cardioplegic solution that was hypocalcemic, alkalotic, hyperosmolar, and enriched with glutamate and aspartate during 1 hour of cardiopulmonary bypass. Of these, six piglets did not undergo hypoxemia (blood cardioplegic control) and 14 others remained hypoxemic (oxygen tension about 25 mm Hg) for up to 2 hours by lowering ventilator fraction of inspired oxygen before reoxygenation on cardiopulmonary bypass. The primary solution of the cardiopulmonary bypass circuit was unchanged in eight piglets (no treatment) and supplemented with the antioxidants N-(2-mercaptopropionyl)-glycine (80 mg/kg) and catalase (5 mg/kg) in six others (N-(2-mercaptopropionyl)-glycine and catalase). Myocardial function (end-systolic elastance), lipid peroxidation (myocardial conjugated diene production), and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest produced no biochemical or functional changes in nonhypoxemic control piglets. Reoxygenation caused an approximate 10-fold increase in conjugated production that persisted throughout cardiopulmonary bypass, lowered antioxidant reserve capacity 86% +/- 12%, and produced profound myocardial dysfunction, because end-systolic elastance recovered only 21% +/- 2%. Supplementation of the cardiopulmonary bypass prime with N-(2-mercaptopropionyl)-glycine and catalase reduced lipid peroxidation, restored antioxidant reserve capacity, and allowed near complete functional recovery (80% +/- 8%).** Lipid peroxidation (conjugated diene) production was lower during warm blood cardioplegic reperfusion than during induction in all reoxygenated hearts, which suggests that blood cardioplegia did not injure reoxygenated myocardium. We conclude that reoxygenation of the hypoxemic immature heart causes cardiac functional and antioxidant damage that nullifies the cardioprotective effects of blood cardioplegia that can be avoided by supplementation of the cardiopulmonary bypass prime with antioxidants (*p < 0.05 vs blood cardioplegic control; **p < 0.05 vs reoxygenation).

Alkadienes↗
PubMed1995

Circulating endothelin in patients undergoing coronary artery bypass grafting.

Increased synthesis of endothelin, (a powerful physiological vasoconstrictor), is a uniform response to endothelial injury and has been associated with myocardial ischemia and reperfusion. This study tests the hypothesis that coronary artery bypass grafting (CABG) affects endothelin plasma concentrations in various vascular beds. Twenty-four CABG patients were included in this study. Endothelin was determined in multiple plasma specimens obtained from superior vena cava, aortic root and coronary sinus (CS). Venous endothelin plasma concentrations collected in CABG patients before surgery were 1.16 +/- 0.18 pg/ml. They increased after sternotomy (1.71 +/- 0.12 pg/ml) and during (2.97 +/- 0.27 pg/ml) and after cardiopulmonary bypass (CPB, 2.72 +/- 0.21 pg/ml). There is no net release of endothelin from the coronary circulation before (aorta 2.26 +/- 0.13 pg/ml vs CS 2.44 +/- 0.17 pg/ml, not significant (n.s.), during (cardioplegia 2.55 +/- 0.17 pg/ml vs CS 2.45 +/- 0.15 pg/ml, n.s.), and after aortic cross-clamping (aorta 2.95 +/- 0.23 pg/ml vs coronary sinus 2.71 +/- 0.18 pg/ml, n.s.). Pulmonary endothelin clearance is preserved on partial bypass (aorta 2.26 +/- 0.13 pg/ml vs vena cava 2.86 +/- 0.18 pg/ml, P < 0.003), but remains inhibited even 10-30 min after release of the aortic cross-clamp (aorta 2.95 +/- 0.23 pg/ml vs vena cava 2.97 +/- 0.27 pg/ml, n.s.). Two out of 24 patients had severe myocardial ischemia. These patients showed particularly high endothelin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Primary cardiac angiosarcoma. A case report.

A primary cardiac malignancy is a very rare diagnosis. The most prevalent malignant cardiac tumors are angiosarcomas. Autopsy specimens, microscopic slides, clinical and intraoperative data from a 72-year-old woman referred to our hospital with a suspected mediastinal tumor were studied. The patient was diagnosed with primary cardiac angiosarcoma by microscopic examination under surgery and underwent resection of the tumor, which compressed and obstructed the right atrium and ventricle. She was discharged from our hospital after 3 weeks and died of right heart failure 2 months after the operation.

Aged↗
PubMed1995

Endothelin during cardiovascular surgery: the effect of diltiazem and nitroglycerin.

To investigate whether the vasoconstrictor peptide endothelin (ET) is elevated during cardiovascular surgery and might predispose to perioperative vasoconstriction and ischemia, we compared the effect of the calcium channel blocker diltiazem with that of the nitric oxide (NO) donor nitroglycerin on ET and hemodynamics in 32 patients undergoing coronary artery bypass grafting (CABG). Following a double-blind protocol, 16 patients (3 women, 13 men; ages 63 +/- 10 years) received 1 microgram/kg/min nitroglycerin and 16 patients (5 women, 11 men; ages 64 +/- 8 years) received 3 micrograms/kg/min diltiazem intravenously 30 min before until 12 h after CABG. ET was measured in the superior vena cava before, during, and 1 h after CABG. Compared with ET levels before CABG, ET was significantly elevated during CABG and further increased after CABG (p < 0.05). During and after surgery, ET levels were lower in patients receiving diltiazem than in those receiving nitroglycerin (both p < 0.01). Mean arterial blood pressure and heart rate were lower in patients receiving diltiazem compared with those receiving nitroglycerin (both p < 0.05). These data demonstrate that diltiazem is more effective than nitroglycerin in preventing ET increase during cardiovascular surgery. Studies using ET receptor antagonists may be useful in assessing the clinical relevance of ET levels with respect to the risk for perioperative vasoconstriction and ischemia.

Aged↗
PubMed1994

Comparison of threshold values between steroid and nonsteroid unipolar membrane leads.

The aim of this study was to evaluate whether steroid membrane leads can reduce pacing thresholds and thereby save energy as compared to nonsteroid membrane leads. The study was a random sample, double blind test consisting of 90 patients between 49-94 years of age admitted to seven hospitals in Europe for pacemaker implantation. The two leads compared in this study had contoured activated carbon tips covered with ion exchange membranes. The leads were identical except that 30 micrograms of dexamethasone was dissolved in the ion exchange membrane of one of the leads. Normal lead implant procedures were used. Follow-up procedures were conducted at 2 weeks and 1, 3, 6, and 12 months after lead implantation. The pulse generator was programmed to an amplitude of 2.5 or 5 V and a duration of 0.5 msec. The stimulation threshold was measured using the VARIO function. The threshold was measured a total of three times in order to determine the presence of microdislocations. At the 2- and 4-week follow-ups, the stimulation threshold was significantly lower for the steroid leads than for the membrane leads without steroid (0.54 +/- 0.19 vs 0.76 +/- 0.25 V, P = 0.0005; and 0.59 +/- 0.19 vs 0.74 +/- 0.26 V, P = 0.005), but after 3 months, the threshold values were almost the same for both leads.

Aged↗
PubMed1994

Reperfusion injury in skeletal muscle: interaction of osmotic and colloid-osmotic pressure in the initial reperfusate for oedema prevention.

Previous studies from the authors' laboratory have shown that controlled limb perfusion after prolonged, acute ischaemia minimizes reperfusion injury. The present study was performed to investigate the role of osmotic and colloid-osmotic pressure in the initial reperfusate in order to reduce postischaemic limb oedema and subsequent reperfusion injury. A total of 96 isolated rat hindlimbs were used: 18 were perfused immediately after amputation (no ischaemia; untreated) and 78 limbs were subjected to 4 h of warm ischaemia in a moist chamber. Thereafter eight limbs were used to investigate the effects of the addition of mannitol to the initial reperfusate. The remaining 70 limbs received controlled reperfusion (modified reperfusate with various osmotic (315-580 mosmol/l) and colloid-osmotic pressure (0-50 mmHg. perfusion pressure 50 mmHg) during the first 30 min after ischaemia. Controlled reperfusion was always followed by uncontrolled reperfusion (30 min. perfusion pressure 100 mmHg) to simulate the clinical condition where normal blood perfusion at systemic pressure will follow controlled reperfusion. Functional recovery, limb weight, water content of the soleus muscle, limb flow and tissue high-energy phosphates were assessed at the end of the experiment. Results show that a reperfusate without colloid-osmotic pressure (i.e. without macromolecules) produces severe limb oedema (84.6(2.0)% water content) and allows no functional recovery after prolonged warm ischaemia. Addition of mannitol to the initial reperfusate does not prevent severe reperfusion injury. In contrast, a hyperosmotic reperfusate with a colloid-osmotic pressure of 26 mmHg effectively prevents limb oedema (78.6(0.9)% water content, 110.8(2.4)% of control weight). Physiological osmotic pressure (315 mosmol/l), however, will not reduce oedema formation (82.7(0.4)% water content). Furthermore, colloid-osmotic pressure > 26 mmHg increases the viscosity of the reperfusate (flow decreases to < 50% of control) and does not allow an optimal functional recovery. Macromolecules used to create the colloid-osmotic pressure should be of similar molecular weight to albumin (69,000 Da); those with a smaller molecular weight (e.g. hydroxyethyl starch40,000/0.5) produce excessive limb oedema (184.9(13.5)% control weight; 85.7(1.4)% water content) without functional recovery (0% control contractions). The present data suggest that after prolonged limb ischaemia: (1) addition of mannitol to a crystalloid solution does not prevent oedema; (2) hyperosmotic reperfusates (380-480 mosmol/l) with a colloid-osmotic pressure of 26 mmHg are most effective in preventing limb oedema; and (3) macromolecules used to achieve colloid-osmotic pressure should have a molecular weight similar to albumin.

Animals↗
PubMed1994

Discordance of anti-ischemic and hemodynamic effects of captopril in stable coronary artery disease.

BACKGROUND: The role of angiotensin converting enzyme (ACE) inhibition in patients with coronary artery disease without concomitant disease such as heart failure or hypertension has not been elucidated. In this double-blind, cross-over, randomized trial of the ACE inhibitor captopril, its antianginal and anti-ischemic effects were studied during monotherapy and in the presence of an organic nitrate. METHODS: Thirty-seven patients (34 men, three women) with stable coronary artery disease and exercise-induced ST-segment depression were enrolled. After a washout phase without medication they received placebo, isosorbide dinitrate (ISDN) 20 mg twice daily, captopril 12.5 mg twice daily, and the combination of both for 1 week each, after which exercise tolerance, blood pressure and heart rate (supine, standing and 24 h profile), and peripheral arterial vasodilatation (finger pulse plethysmography) were assessed. RESULTS: Thirty-three patients completed all phases of the study. Exercise-induced anginal symptoms occurred in 17 patients, and asymptomatic ischemia was seen in the other 16 men. In comparison with ISDN, the anti-ischemic effects of captopril were minimal, despite a similar reduction in blood pressure. Compared with baseline, 1 week of placebo reduced the sum of ST-segment depression, the main efficacy parameter, by 10% (NS), captopril by 19% (NS), ISDN by 37% (P < 0.001) and the combination of captopril and ISDN by 42% (P < 0.001; NS versus ISDN). No patient remained completely free of exercise-induced angina during treatment with captopril; however, three patients after ISDN and seven patients after the combination did (P < 0.05). Blood pressure at rest decreased at peak effect by 9-10% systolic (P < 0.001) with monotherapy and by up to 7% diastolic (P < 0.001), and during combined therapy with captopril and ISDN by 18% systolic (P < 0.001) and 12% diastolic (P < 0.001). Significantly enhanced circulatory effects of captopril plus ISDN versus ISDN were found for blood pressure (P < 0.001) and peripheral arterial vasodilation (P < 0.01). The reflex tachycardia induced by ISDN in the upright position (5 beats/min) was not blocked by captopril during combined therapy. CONCLUSIONS: The antianginal and anti-ischemic effects of captopril alone were marginal, despite significant circulatory effects after short-term administration. Although captopril in combination with ISDN resulted in a significant further blood-pressure-lowering effect and increased peripheral arterial vasodilatation, the magnitude of potentiation of the anti-ischemic nitrate effects was, in contrast, small. Only exercise-induced angina was further improved by the use of the combination. No paradoxical worsening of ischemia or angina was seen after captopril. Thus, although captopril has no place as first-line therapy for ischemia, its use in combination with ISDN could be advantageous for long-term prognosis.

Aged↗
PubMed1994

Early and long-term results of cardiac surgery in dialysis patients.

Cardiac surgery in patients receiving dialysis has a high mortality and morbidity. Early long-term results have been analysed following various cardiac operative procedures. Between 1981 and 1992, 40 patients, of mean age 55.7 (range 31-71) years underwent cardiac surgery. Procedures included coronary artery bypass grafting (20 patients), aortic valve replacement (six), mitral valve replacement (four), aortic valve or mitral valve plus coronary artery bypass grafting (one each), aortic plus mitral valves (two), heart and renal transplantation (one each), atrial septal defect closure (one) and pericardial decortication (three). Before surgery, patients were in the New York Heart Association (NYHA) classes II (5%), III (52.2%) and IV (42.5%). The operative mortality rate was 15%; survivors were in NYHA classes I (3%), II (88.2%) and III (8.8%). There were 11 late deaths. Follow-up at a mean of 35 (range 1-93) months showed actuarial survival rates of 91% (1 year) and 69% (5 years). After coronary artery bypass grafting, survival rates were 95% (1 year) and 72% (5 years). Survivors were in NYHA classes I (4.7%), II (85.5%) and III (9.5%). Cardiac surgery in dialysis patients is associated with an acceptable hospital mortality; quality of life in long-term survivors is increased. Hence, surgical treatment is advocated in patients with symptomatic heart disease. Early diagnosis and surgical intervention in NYHA class II patients may lead to a lower perioperative mortality.

Adult↗
PubMed1993

Cardiopulmonary dysfunction produced by reoxygenation of immature hypoxemic animals supported by cardiopulmonary bypass. Prevention by intravenous metabolic pretreatment.

This study tests the hypothesis that reoxygenation injury is produced when cardiopulmonary bypass is initiated in immature hypoxemic piglets and that it causes cardiopulmonary dysfunction that can be avoided by intravenous metabolic treatment before and during cardiopulmonary bypass. Of 18 immature Yorkshire-Duroc piglets (aged < 3 weeks), six were anesthetized, instrumented, and observed for 5 hours (control animals). Twelve piglets underwent up to 2 hours of hypoxemia (arterial oxygen tension = 20 to 30 mm Hg) before initiation of reoxygenation on cardiopulmonary bypass. Six received an intravenous metabolic infusion solution (mercaptopropionyl glycine, catalase, aspartate, glutamate, glucose/insulin), which was started before and continued during cardiopulmonary bypass. Hypoxia produced an initial hyperdynamic response (39% increase in cardiac index; p < 0.05) followed by progressive hemodynamic deterioration, necessitating premature initiation of bypass in 8 of 12 hypoxemic piglets (67%). Reoxygenation-induced injury (assessed 30 minutes after cardiopulmonary bypass) was characterized by 39% reduction of stroke work index (p < 0.05), increased myocardial lipid peroxidation (79% increase of conjugated dienes; p < 0.05), 254% increase in pulmonary vascular resistance index (p < 0.05), 22% decrease in static lung compliance (p < 0.05), and 50% decrease in arterial/alveolar oxygen tension ratio (p < 0.05). These reoxygenation changes were avoided by intravenous metabolic treatment. We conclude that the reoxygenation of immature hypoxemic piglets by initiating cardiopulmonary bypass results in cardiopulmonary dysfunction that may increase vulnerability to subsequent ischemia (i.e., aortic crossclamping). The cardiopulmonary reoxygenation changes are preventable by intravenous metabolic treatment before and during cardiopulmonary bypass needed for cardiac repair.

Animals↗
PubMed1992

The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function.

The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.

Adrenergic Agonists↗
PubMed1992

Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery.

We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2-adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (1, 2, 4 and 6 micrograms.kg-1.min-1), the dose producing the optimal response was infused for up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean blood pressure was reduced but did not fall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac output following cardiac surgery.

Adrenergic Agonists↗