Comparison of early and late mortality in men and women after isolated coronary artery bypass graft surgery in Stockholm, Sweden, 1980 to 1989.

OBJECTIVES: We sought to analyze early and late mortality after coronary artery bypass graft surgery (CABG) in relation to gender. BACKGROUND: Early mortality after CABG is generally higher in women than in men, but the causes are controversial. Few studies have investigated long-term mortality after CABG in relation to gender. METHODS: In all, 3,326 men and 607 women underwent isolated CABG in Stockholm from 1980 to 1989. Mortality for these patients was followed by means of the National Cause of Death Register, from the time of operation until the end of 1990. Survival was evaluated by life-table methods and by proportional hazards regression. RESULTS: Early mortality (within 30 days) was 3% in women and 1.7% in men, corresponding to a relative risk of 1.8 (95% confidence interval [CI] 1.0 to 3.0) in women compared with men. When age and body surface area were taken into account, the relative risk was 1.0 (95% CI 0.5 to 2.0), which was not markedly different but multivariate analyses that included hypertension, diabetes mellitus, previous myocardial infarction, left ventricular function and number of diseased vessels. Only small gender differences in mortality were observed for 5 years after the operation among those who survived for 30 days. CONCLUSIONS: The results suggest that men and women run similar risks of early and late mortality after CABG when patient characteristics are taken into account.

Are geographical differences and time trends in myocardial infarction incidence in Sweden real? Validity of hospital discharge diagnoses.

In Sweden, acute myocardial infarction (AMI) incidence has been found to differ considerably between the neighboring counties of Stockholm and Gävleborg, with an increase in Stockholm during the 1970s. We estimated the AMI incidence in Stockholm in 1973 and in both areas in 1981. To determine if there were differences in the validity of hospital discharge diagnoses, random samples of AMI patients were examined for diagnostic criteria for AMI. In both genders, AMI incidence was higher in Gävleborg than in Stockholm (relative risk (RR) 1.34 for men and 1.21 for women) and increased in Stockholm from 1973 to 1981 (RR 1.21 for men and 1.29 for women). The proportion of patients fulfilling the diagnostic criteria for AMI was similar in both areas in 1981 but 10% less in Stockholm in 1981 than in 1973. These results suggest that differences in the validity of hospital discharge diagnoses cannot explain the geographical differences in AMI incidence, but that this may have contributed to the increasing incidence seen in Stockholm county.

Time trends in survival from myocardial infarction in Stockholm County 1976-1984.

In Stockholm county, a rapid decline in mortality from acute myocardial infarction (AMI) was observed among middle-aged men in the early 1980s. In the present study survival among AMI patients from 1976 to 1984 was investigated in order to explore whether improvements in survival may have contributed to this decline. AMI patients aged 30-74 years (n = 16,108) were identified through a hospital discharge register. Deaths within one year of hospital admission were ascertained by means of linkage to the national cause of death register. Survival 1 year after hospital admission increased in both genders during the period 1981-1984, but among women there was no uniform trend over the whole study period. The estimated age-adjusted relative risk of death within one year after hospital admission for patients with a first infarction admitted to hospital in 1983-1984 as compared to in 1981-1982 was 0.88 for men and 0.79 for women. The causes of the observed increase in survival could not be determined from this study, but changes in medical intervention as well as diagnostic improvements may have been important. Improved survival may have contributed to about 30% of the decline in mortality from AMI among middle-aged men in Stockholm county during the early 1980s.

Factors influencing tolerance to the effects of delta9-THC on a conditioned avoidance response.

Male, Fischer strain rats were resistant to the impairing effects of delta9--THC (15-60 mg/kg, IG) on performance of a conditioned pole-climb avoidance response (CAR) after daily subacute pretreatment for 4 or 6 days. A single administration of 20 mg/kg delta9--THC independent of the performance test did not attenuate the subsequent impairment caused by delta9--THC when tested 1-6 days later; however, administration 2 hr before each test attenuated the effect on subsequent tests given at intervals of 1-5 weeks. Similarly, subacute treatment with 20 mg/kg delta9--THC for 4 days independent of the performance test attenuated the impairment caused by delta9--THC during tests given to separate groups of rats 1 or 6, but not 14 days later. However, when the tests for tolerance were conducted repeatedly in the same rats, the attenuation appeared to persist for intervals up to 5 weeks. The results are discussed in terms of metabolic, functional and compensatory (behavioral) tolerance.

Interactions of delta9-tetrahydrocannabinol with d-amphetamine, cocaine, and nicotine in rats.

The acute, reciprocal dose-response interactions between delta9-tetrahydrocannabinol (delta9-THC; 2.5, 5.0 and 10.0 mg/kg; IG) and each of three stimulants - d-amphetamine (dA; 1, 2 and 4 mg/kg; IP), cocaine (COC; 10, 20 and 30 mg/kg; IP), and nicotine (NIC; 0.25, 0.5 and 1.0 mg/kg; IP) were studied for their effects on performance of a conditioned avoidance response (CAR), photocell activity, heart rate, body temperature, and rotarod performance. delta9-THC impaired CAR and rotarod performance, depressed photocell activity, and decreased heart rate and body temperature. None of the three stimulants influenced CAR performance, but dA and COC increased the number of intertrial responses, and this latter effect was partially antagonized by delta9-THC. dA and COC, but not NIC, stimulated photocell activity. delta9-THC completely blocked this effect of dA, whereas there was mutual antagonism between delta9-THC and COC on this measure and NIC markedly potentiated the depression caused by delta9-THC. dA and COC tended to offset the impairment of rotarod performance caused by delta9-THC, whereas NIC augmented it. The bradycardia and hypothermia caused by delta9-THC tended to be augmented by these stimulants, especially NIC. The interactions were also studied after subacute treatment for six days with delta9-THC and/or each of the three stimulants. There was evidence for tolerance to the effects of delta9-THC on all measures and this tolerance generally resulted in less interactive effects between delta9-THC and the stimulants. Little or no tolerance was seen for the effects of the three stimulants or their interaction with delta9-THC. The time course of radioactivity derived from 14C-delta9-THC and each of the radiolabelled stimulants was determined in plasma and brain. Only minor interactive effects were found and, in general, they could not account for the functional interactions.

The effects of beta blockade with (epanolol) and without (atenolol) intrinsic sympathomimetic activity in stable angina pectoris. The Visacor Study Group.

Beta blockade constitutes efficient therapy for stable angina pectoris. The effects of lowering blood pressure and heart rate with such treatment are not always desired. Epanolol is a beta 1-selective partial agonist with minor effects on blood pressure and heart rate at rest. Atenolol is a pure beta 1-selective antagonist with more pronounced effects on blood pressure and heart rate at rest. The effects of epanolol, 200 mg o.d., and atenolol, 100 mg o.d., were compared in 173 middle-aged patients with stable angina pectoris in a randomized, double-blind, parallel group-controlled study for one year. No significant differences were shown in angina attack rate, nitrate consumption, or exercise performance. Resting heart rate and blood pressure were significantly lower on atenolol. Epanolol tended to be better tolerated than atenolol, as shown by visual analogue scales of well-being, activity, energy, and warm extremities, further supported by fewer reports on possible adverse reactions. In conclusion, epanolol appears to be as effective as atenolol and better tolerated in patients with stable angina pectoris.

Exercise performance and beta-adrenergic blockade in patients with complete heart block treated with ventricular inhibited pacing.

The effect of beta-adrenergic blockade (propranolol) on exercise performance was studied in 15 patients (12 men and 3 women, mean age 70 years) with complete heart block treated with a ventricular-inhibited pacemaker (VVI). In a double-blind procedure, the patients were randomly given either 0.1 mg/kg of propranolol or saline solution i.v. before a first exercise test and vice versa before a second test. The interval between the tests was 24 hours. Nine patients were in sinus rhythm, 4 patients had atrial flutter, and 2 others had atrial fibrillation. The exercise capacity was on an average 11% lower with propranolol than with placebo (p less than 0.001). The most marked reductions (20 and 33%) were found in the two patients with atrial fibrillation. The atrial rate in patients with sinus rhythm was significantly lower with propranolol than placebo both at rest (68 vs. 83 beats/min, p less than 0.001) and at maximal work load (91 vs. 141 beats/min, p less than 0.001). The present findings show that beta blockade has negative effects on exercise capacity in patients with complete heart block treated with VVI pacemakers. This finding should be considered in the selection of drug treatment in patients with fixed rate pacing and concomitant hypertension and/or ischemic heart disease.

Effects of furosemide and slow-release furosemide on thoracic fluid volumes.

Transthoracic electrical impedance (TEI) was used to assess the relative effectiveness of a 60 mg sustained-release furosemide preparation (FR) and a 40 mg standard furosemide tablet (F), in reducing the fluid content in the thoracic cavity. A double-blind crossover study was performed, in which 12 men with a history of one or more myocardial infarctions and mild left heart failure treated with 40 mg furosemide once daily participated. The trial, lasting 28 days, was divided into two 14-day periods. Each participant received one active drug and one placebo preparation daily, the same regimen being maintained for 14 days, when the active substances were switched. TEI, body weight, serum potassium, sodium, creatinine, and urate were measured immediately prior to the start of the study, after 14 days, and at the end of the study. TEI was measured at frequencies of 1 and 100 kHz with a constant current of 100 microA, during a period of one hour following an intravenous injection of 40 mg furosemide, when the urine volumes were measured also. TEI and urine production after the furosemide injections were similar irrespective of the drug preparation. No evidence of treatment period interaction was seen. No significant differences were demonstrated in body weight and blood chemistry during the trial. These results suggest clinical equipotency of the two preparations in mild left heart failure.

Release characteristics of enzymes used in the diagnosis of myocardial infarction.

Release characteristics of S-LD, S-LD1, S-ASAT, S-CK and S-CK-MB were studied in 47 consecutive AMI patients. In addition, previously obtained data for serum myoglobin (S-MYO) were compared. Serum was sampled at regular intervals after admission to the Coronary Care Unit (CCU). The release rate and half lives of the enzymes were calculated according to a one-compartment kinetic model. The time to peak values, the time of total release and the half lives were interrelated in the following order: MYO less than CK-MB less than CK less than ASAT less than LD1 less than LD which coincides with the wellknown appearance and disappearance rates in serum. The ratio between mean peak values and upper reference limits followed the reverse order. The finding that the release rate of enzymes and half-lives co-vary is hypothetically suggested to be attributed to differences in rate of membrane diffusion. There is indirect evidence that a slow indicator such as LD1 reflects infarct size better than fast indicators with rapid release and removal such as MYO or CK-MB. However, these fast markers have a better signal to noise ratio, whereby they probably reflect changes in the infarction process better.

Hemispheric asymmetries in a signal detection task.

Reaction time and signal detection performance were measured during a 78-min. vigilance task. 12 right-handed male subjects served in two experimental sessions. Subjects focused on a central fixation point and responded to signals presented at unpredictable times in one of three locations: 2.5 degrees to right of central fixation, central, and 2.5 degrees to the left of center. Subjects decided whether to press a response key with either the left or right hand with each presentation. Over-all vigilance performance (signal detections and response time) was similar for left and right visual-field presentations. Evidence from reaction times indicated that responses controlled by the left hemisphere were faster to a verbal stimulus (T) while reactions controlled by the right hemisphere were faster to an apparent non-verbal stimulus, an inverted T.

Influence of spontaneous pursed lips breathing on walking endurance and oxygen saturation in patients with moderate to severe chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate how spontaneously used pursed lips breathing influences walking endurance, oxygen saturation and dyspnoea in patients with moderate to severe chronic obstructive pulmonary disease. DESIGN: A randomized open-label, cross-over study of chronic obstructive pulmonary disease patients participating in a rehabilitation programme. SETTING: Outpatient pulmonary rehabilitation centre at a university hospital. SUBJECTS: Thirty-two patients with moderate to severe chronic obstructive pulmonary disease. INTERVENTION: All patients performed two endurance shuttle walking tests in random order. During endurance shuttle walking test I a mouthpiece was used in order to prevent spontaneous pursed lips breathing. During endurance shuttle walking test II spontaneous pursed lips breathing was used freely. Heart rate, oxygen saturation and the patients' estimated dyspnoea and leg fatigue on a Borg Category Ratio 10 scale were recorded before, directly after, and 5 and 10 minutes after the tests. RESULTS: When spontaneous pursed lips breathing was used the patients walked on an average for 37 seconds (16%) longer (P<0.01) than when pursed lips breathing was prevented. The patients desaturated considerably during both walking tests but the average drop in oxygen saturation was 1.2% less when spontaneous pursed lips breathing was employed. There were no significant differences in rated degree of dyspnoea or leg fatigue with or without pursed lips breathing. CONCLUSION: Spontaneous pursed lips breathing can be a useful technique to increase walking endurance and reduce oxygen desaturation during walking in patients with moderate to severe chronic obstructive pulmonary disease.

Haemodynamic effects of high or low doses of furosemide in acute myocardial infarction.

The haemodynamic effects of high or low doses of furosemide used to prevent overt left heart failure (LHF) in acute myocardial infarction (AMI) were studied. Fifteen consecutive AMI patients without overt LHF and with a cardiac index (CI) of 2.6 +/- 0.5 l min-1 m-2, a right atrial mean pressure (RAMP) of 7 +/- 3 mmHg and a pulmonary arterial diastolic pressure (PADP) of 14 +/- 4 mmHg were investigated during 24 h. A high dose group (HDG) received 40 mg furosemide t.i.d. and a low dose group (LDG) 20 mg once daily. Following the first 40 mg of furosemide (HDG), the stroke volume index (SVI), CI, RAMP and PADP decreased. The heart rate and systemic vascular resistance index (SVRI) increased. Following the first 20 mg of furosemide (LDG), the only significant change was a decrease in PADP. After 24 h, the heart rate in the HDG was further increased; the SVI, RAMP and PADP were further reduced, whereas CI was similar to that before. In the LDG, the heart rate, SVI and CI remained unchanged. All pressures tended to decline and the SVRI was lower than in the HDG. Thus, repeated injections of 40 mg of furosemide induced a sustained preload reduction in AMI patients without overt LHF, but this was associated with potentially disadvantageous haemodynamic findings.

Prophylactic furosemide treatment in acute myocardial infarction.

Prophylactic diuretic therapy in acute myocardial infarction (AMI) was evaluated in 83 consecutive patients without severe left ventricular failure (LVF) on admission. A high dose group (HDG) received 120-160 mg and a low dose group (LDG) 20-40 mg furosemide daily for six weeks. Mortality and reinfarction rates did not differ between the groups. One HDG patient and five LDG patients developed severe LVF. Four HDG patients developed severe dehydration. Serum enzyme activities and electrolytes were similar in both groups. The increased diuresis in the HDG was accompanied by a 4% hemoconcentration, smaller radiological heart volumes, higher heart rates, a higher demand for nitroglycerin and higher ratings of thirst. Exercise tests yielded similar results in both groups. Later blood volumes and transthoracic electrical impedance were similar in both groups. It is concluded that liberal prophylactic furosemide treatment in AMI offers no major clinical advantage.

Influence of prophylactic furosemide on arrhythmias in acute myocardial infarction--a controlled study.

In a prospective controlled study the frequency of arrhythmias during the early phase of acute myocardial infarction (AMI) was evaluated in 73 consecutive patients randomly assigned to either high or low dose furosemide prophylaxis. The high dose group (HDG) received 120 mg and the low dose group (LDG) 20 mg furosemide i.v. during the initial 24 hours in hospital. Increased diuresis, haemoconcentration and augmented heart rates were found in the HDG. No electrolyte disorders separated the groups. Hypokalemia was seen in two HDG patients and in one LDG patient on admission, and in two and three patients respectively after 24 hours. Continuous ECG recordings at a paper speed of 10 mm s-1 were obtained from all patients. Two patients in the HDG had ventricular fibrillation, none in the LDG. The number of patients with various arrhythmias was not significantly different in the two groups. Supraventricular tachyarrhythmias were more common in the HDG, whereas ventricular tachycardia and ventricular extrasystoles were seen more often in the LDG. We conclude that heart rate and recurrence of tachyarrhythmias in AMI may be influenced by furosemide therapy, seemingly through mechanisms other than electrolyte imbalance.

Nitric oxide improves hypoxaemia following reperfusion oedema after pulmonary thromboendarterectomy.

A patient underwent pulmonary thromboendoarterectomy for chronic, major-vessel thromboembolic pulmonary hypertension. After operation the patient developed reperfusion oedema and hypoxaemia which was treated successfully with inhalation of nitric oxide. Before operation, the response to inhaled nitric oxide was characterized by a slight reduction in pulmonary vascular resistance but without improvement in gas exchange. The postoperative improvement in oxygenation after inhalation of nitric oxide contrasted sharply with the preoperative reaction.

Transthoracic electrical impedance at 1 and 100 kHz--a means for separating thoracic fluid compartments?

The electrical impedance of biological tissues varies with their water and electrolyte contents. Alternating current above 5-10 kHz passes both intra- and extracellular fluid, and lower frequency current preferentially extracellular fluid. In an attempt to evaluate thoracic fluid in different compartments, transthoracic electrical impedance (TEI) was measured at 1 and 100 kHz in 15 consecutive patients, without overt left heart failure and under haemodynamic surveillance, during the first two days of myocardial infarction. To achieve different states of hydration the patients were given i.v. furosemide, either 40 mg t.i.d. (high dose group--HDG) or 20 mg once daily (low dose group--LDG). Effects of altered body position and the respective furosemide injections, were evaluated on both days. Mean 24-h-diuresis was 3.9 l in the HDG and 2.5 l in the LDG. After 24 h mean pulmonary arterial diastolic pressure had decreased by 30% in the HDG but remained almost unchanged in the LDG. By then mean basal TEI was increased only in the HDG, by 17% at 1 kHz and 13% at 100 kHz. On Day 1, within one hour after furosemide, TEI increased temporarily by 3-5%, at both frequencies and in both groups. On Day 2, this short-term increase was similar in the LDG at both frequencies and in the HDG at 100 kHz, but not at 1 kHz, consistent with a major extracellular fluid loss in the HDG. TEI at 1 and 100 kHz may thus reflect extracellular and total thoracic fluid, respectively.

ET-1 infusion increases systemic vascular resistance and depresses cardiac output in patients with chronic hypoxaemia and pulmonary hypertension.

The pulmonary vascular effects of the endothelium-derived peptide endothelin (ET) vary depending on the existing vascular tone, modes of administration and species studied; ET can cause both pulmonary vasodilatation and vasoconstriction. Increased plasma levels of ET have been reported in hypoxic pulmonary hypertension, although it is unclear whether ET is a mediator or a marker of hypoxia-induced increase in pulmonary vascular resistance (PVR). In our study, the plasma levels of ET-1 and the functional effects of ET-1 infusion in patients (n = 4) with chronic hypoxaemia and elevated PVR were evaluated. At rest, the arterial and venous ET-1-levels (13 +/- 2 and 12 +/- 1 fmol/ml, respectively) were significantly higher than those detected in venous plasma of an age-matched healthy control group (7 +/- 1 fmol/ml). Consecutive 10 min infusions of ET-1 at 1, 5, 10 and 15 ng/kg/min into the pulmonary artery decreased cardiac output (by 32%) and stroke volume (by 33%) and increased the systemic vascular resistance (by 62%) and arteriovenous oxygen difference (by 83%) at the highest dose. No deleterious effect was observed in the pulmonary circulation. The present study therefore suggests that intra-pulmonarily administered ET does not attenuate the increased PVR associated with chronic hypoxaemia.

Long-term comparison of the electrical characteristics of polyurethane and polyethylene insulated ventricular leads.

Two types of pacing leads with different insulation material, polyurethane, and polyethylene, were followed for 44 months with respect to their electrophysiological characteristics and complications. In 48 patients, 32 polyurethane leads (Lifeline 493-03) and 16 polyethylene leads (EMT 588 D) were implanted and connected in all cases to the same type of programmable ventricular inhibited (VVI) pulse generator (Programalith, Pacesetter). There was a significant fall during the follow-up in lead impedance with the polyurethane leads (495 +/- 62 to 444 +/- 58 ohms, P less than 0.01), whereas the corresponding measurements for the polyethylene leads were essentially unchanged (360 +/- 58 to 378 +/- 71 ohm, ns). The energy of the stimulation threshold tended to increase in the polyurethane group, whereas an opposite tendency was observed in the polyethylene group. Pacing and/or lead failures were not observed in any case. The observed fall in impedance with the polyurethane leads was seemingly of no clinical significance.

Determination of cardiac involvement in sarcoidosis by magnetic resonance imaging and Doppler echocardiography.

OBJECTIVES: To elucidate whether cardiac magnetic resonance imaging (MRI) could be useful in disclosing structural changes in the myocardium in sarcoidosis patients and to relate echo-Doppler derived indices of left ventricular function to electrocardiogram (ECG) findings. DESIGN: The MRI was performed in 18 consecutive patients with sarcoidosis. Left ventricular ejection fraction (LVEF), i.e. systolic function, was estimated echocardiographically by Simpson's two-dimensional method (n = 16). Diastolic function was estimated by age-corrected Doppler-derived indices: isovolumetric relaxation time (IVRT), deceleration time (DT) and early filling/atrial contraction ratio (E/A ratio). RESULTS: Eleven patients had conduction defects or dysrhythmias (ECG+) whilst seven patients had a normal ECG (ECG-). In two patients, high signalling, contrast-enhanced, isolated regions, suggestive of deposits, were seen in the left ventricular myocardium on MRI. Both these patients had abnormal ECGs and signs of systolic and/or diastolic dysfunction on echocardiography. LVEF was subnormal in seven of 10 of the ECG+ patients and in two of six of the ECG-. Signs of diastolic dysfunction were found in 59% and 56% of the measurements in the ECG+ and ECG- patients, respectively. CONCLUSION: We conclude (i) that myocardial deposits on MRI in sarcoidosis patients have a high specificity for cardiac involvement but a rather low sensitivity; (ii) that a substantial proportion of sarcoidosis patients with abnormal ECGs have echocardiographic signs of systolic and/or diastolic dysfunction.