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J Hultman

Publications and source records attributed to J Hultman.

At least 37 records · Page 2Linked to original sources

Influence of adenosine on left ventricular performance in conscious dogs.

Adenosine, a potent vasodilator of both the peripheral and coronary vasculature, is increasingly used to produce controlled hypotension in the clinical and experimental setting. To define the influence of adenosine on left ventricular (LV) performance in conscious closed-chest dogs were studied six chronically instrumented autonomically blocked animals before and after the administration of 0.3, 0.6, and 1.2 microM.kg-1.min-1 infusions of adenosine. Systolic performance was quantified by the end-systolic pressure-volume (Pes-Ves) and stroke work end-diastolic volume (SW-EDV) relations. Active diastolic performance was quantified by the time constant of LV relaxation (T), whereas passive diastolic properties were assessed by comparing LV pressures at a common LV volume. Despite a decrease of mean arterial pressure of 51 mmHg, adenosine did not change the slope of the Pes-Ves relation or the end-systolic volume at a pressure of 100 mmHg. The slope of the SW-EDV relation was also unchanged, and its volume axis intercept was slightly reduced. There were no differences in T or in the diastolic pressure at a common LV volume. Thus adenosine appears to have little influence on systolic or diastolic LV performance aside from its marked affect on afterload, indicating it is a useful agent for producing controlled hypotension.

Adenosine↗

Thoracic paravertebral block: a method of pain control.

The adverse effects of pain on acutely ill or traumatized patients are well documented. A variety of pain-relieving techniques are now available to meet the varied requirements for pain relief. This paper presents the results of a single, large-volume injection of bupivacaine 0.5% in the thoracic paravertebral space, achieving pain relief over several thoracic dermatomes in patients with respiratory compromise secondary to thoracic or upper abdominal injury. The block proved quick and simple to perform, with excellent clinical results of long duration and virtually no complications. Although not previously described, this single, large-volume injection approach to achieving an extensive thoracic paravertebral block may well become an important pain management technique in appropriate patients.

Abdominal Injuries↗

Improved myocardial protection by creatine phosphate in cardioplegic solution. An in vivo study in the pig during normothermic ischemia.

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

Animals↗

Functional effects of phosphoenolpyruvate and ATP on pig hearts in cardioplegia and during reperfusion. An in vivo study with cardiopulmonary bypass.

The effects of phosphoenolpyruvate (PEP) and ATP in cardioplegia and during early reperfusion were studied in pigs. Twenty pigs divided into three groups were placed on cardiopulmonary bypass and subjected to 2 h of hypothermic cardioplegic arrest. Group I (n = 7) served as a control. In group II (n = 7) PEP (14.4 mM) and ATP (0.067 mM) were added to the cardioplegic solution. Group III (n = 6) was given PEP (28.8 mM) and ATP (0.134 mM) with 500 ml of isotonic NaCl in the aortic root during early reperfusion. All animals in group III were weaned from bypass compared with 6 of 7 in group I and 5 of 7 in group II. Forty minutes after ischemia group III was assessed to be the only group with an unchanged aortic flow and stroke volume. The total peripheral resistance and arterial pressure were reduced in this group. The results demonstrate that PEP and ATP administered during reperfusion have a beneficial effect and that this may be exerted both on the myocardium and on the peripheral vessels.

Adenosine Triphosphate↗

Myocardial high-energy phosphates, lactate and pyruvate during moderate or severe normothermic ischemia in rat hearts perfused with phosphoenolpyruvate and ATP in cardioplegic solution.

Rat hearts were subjected to normothermic ischemia for 15 min (group I) or 30 min (group II). During the ischemic period the hearts were perfused twice with cardioplegic solution supplemented with 14.4 mM phosphoenolpyruvate (PEP) and/or 0.067 mM adenosine triphosphate (ATP), and at the end of ischemia they were freeze-clamped. The myocardial ATP content in group I fell to about 55% of normal values except in hearts supplemented with only PEP, which showed greater reduction. In group II the ATP fell to only about 5% of normal values, without significant differences between the subgroups Hearts supplemented with PEP alone or with combined PEP-ATP showed significantly higher levels of pyruvate than in hearts with only ATP supplementation or control hearts. The study thus demonstrated clear difference in ATP content between moderate and severe ischemic trauma. The high pyruvate levels after PEP supplementation indicate formation of pyruvate without concomitant lactate increase.

Adenine Nucleotides↗

Interrelated effects of nucleoside mono- and triphosphates and phosphoenolpyruvate on rat hearts subjected to cardioplegic arrest at normothermia.

Supplementation with phosphoenolpyruvate (PEP) and ATP was previously found to enhance the protective effect of potassium cardioplegia on rat hearts subjected to extensive ischemic trauma (30 min at 37 degrees C) in the paracorporeal rat heart model. In the present experiments, the ischemia time was reduced to 20 min (37 degrees C). Ventricular work after ischemia was best in control rats with potassium cardioplegia only. Supplementing the cardioplegic solution with PEP and ATP (group I) resulted in significantly reduced postischemic ventricular work and increased efflux of the creatine kinase isoenzyme MB (CK-MB). The same result was obtained when adenosine monophosphate (AMP) was added to the supplementation (group II). When guanosine monophosphate (GMP) was added instead of AMP (group III), the negative effects of PEP and ATP in the cardioplegic solution were partly abolished. Plain potassium cardioplegia, without additives, nevertheless gave the best results. There were no significant intergroup differences in the myocardial content of adenine nucleotides. The results contrasted with those in the previous study of more protracted ischemic trauma (30 min at 37 degrees C) and possible explanations are discussed.

Adenosine Monophosphate↗

Metabolic and functional effects of creatine phosphate in cardioplegic solution. Studies on rat hearts during and after normothermic ischemia.

Creatine phosphate is a precursor molecule for ATP synthesis, even under ischemic conditions. We investigated its functional and metabolic effects when added to cardioplegic solution. Rat hearts were subjected to normothermic ischemia for 15 or 30 min and then freeze-clamped. During ischemia there was gradual reduction of high-energy phosphates, but the hearts with creatine phosphate supplement showed higher myocardial content of ATP and of the creatine compound. Other hearts, subjected to 20 min of ischemia, were reperfused with blood for 40 min. Creatine phosphate supplementation resulted in better left ventricular isovolumic work during spontaneous activity, but in paced activity (400 beats/min) no significant differences were seen. After reperfusion, supplemented hearts showed a tendency to higher levels of ATP and creatine phosphate. In all three groups the hearts with cardioplegic supplement had significantly increased myocardial content of pyruvate without proportional lactate increase. The results indicate that creatine phosphate may be an effective constituent in cardioplegic solution.

Animals↗

Enhanced protection of rat hearts during ischemia by phosphoenolpyruvate and ATP in cardioplegia.

The paracorporeal rat heart model was used to investigate the extent of myocardial protection by potassium cardioplegia supplemented with phosphoenolpyruvate (PEP) (14.4 mM) and ATP (0.067 mM) singly or in combination. Rat hearts were subjected to 30 minutes of ischemia at 37 degrees. They were subsequently reperfused for 40 minutes during which time the left ventricular isovolumic work was measured and blood samples were taken for creatine kinase isoenzyme MB (CK-MB) analysis. At the end of each experiment the hearts were freeze-clamped for later analyses of high energy phosphate compounds. Supplementation with PEP and ATP (Group I) and with only ATP (Group II) showed a significantly better left ventricular isovolumic work and a significantly higher adenylate charge potential (ACP). Supplementation with only PEP (Group III) resulted in significantly better left ventricular isovolumic work than the control group but significantly lower than groups I and II. There were no significant differences between the groups in regard to the CK-MB efflux. Supplementation with PEP and ATP in combination did not show any positive effect at 40 minutes of reperfusion over and above that which was achieved with ATP only.

Adenosine Triphosphate↗

Myocardial energy metabolism during mitral valve replacement.

To elucidate the metabolic changes during a relatively short ischemic period, papillary muscle excisions were investigated in 38 patients operated for mitral valve replacement. The overall mean age was 62 years, in 27 women and 11 men. Two excisions were made during ischemia, the first after 13 minutes and the second after 48 minutes of aortic occlusion. These excisions were analyzed for adenine nucleotide, creatine phosphate, lactate and pyruvate contents. The results indicated an ongoing metabolism with an accumulation of lactate, and also influences on the energy charge. For example, although the content of ATP was unchanged between the excisions, the relation to creatine phosphate, as a source for ATP level maintenance, was altered. This is of clinical importance since cardioplegia and hypothermia (myocardial temperature below 20 degrees C) were employed and the interval between the excisions was only 35 minutes on average. Although no significant decrease in myocardial ATP took place, 31 of 38 patients needed inotropic support to wean them off bypass. On the basis of the present results further efforts seem necessary to improve myocardial preservation techniques.

Adenine Nucleotides↗

Metabolic and functional effects of phosphoenolpyruvate and adenosine triphosphate on rat hearts subjected to global ischemia.

The effect of phosphoenolpyruvate (PEP) and adenosine triphosphate (ATP) administered during ischemia was investigated, using the paracorporeal rat heart model. During 15 min of global ischemia the hearts were perfused twice with PEP and ATP (supplemented) or with NaCl only (non-supplemented). In hearts that were freeze-clamped after the ischemic period (group A), the myocardial content of high-energy phosphates showed only minor differences between hearts with and without supplemention. In the supplemented hearts there was increased myocardial content of pyruvate and, to some extent, of lactate, indicating that PEP was metabolized to pyruvate and partly to lactate. In groups B and C the hearts were reperfused for 40 min before freeze-clamping. The non-supplemented hearts showed higher energy content and better left ventricular performance and, concomitantly, the creatine kinase isoenzyme MB (CK-MB) efflux was less than for the supplemented hearts. A clear inverse relationship between left ventricular performance and CK-MB efflux indicated that CK-MB served as a marker of cell integrity. These results contrasted with previus finding of an unequivocally positive effect from PEP and ATP administration. Possible explanations are discussed.

Adenosine Triphosphate↗

Myocardial pyruvate, lactate, and orthophosphate contents under different postischemic conditions. A study in a paracorporeal rat heart model.

The myocardial contents of pyruvate, lactate and orthophosphate after ischemia were investigated in a paracorporeal rat heart model under different conditions. The arterial blood was supplemented with phosphoenolpyruvate (PEP) and adenosine triphosphate early during reperfusion of excised hearts subjected to 15 min of complete global ischemia at 37 degrees C. The increase in myocardial pyruvate was significant after 4 min of reperfusion compared with the content in non-supplemented hearts subjected to the same ischemic trauma. Such dynamic changes were not observed for lactate and orthophosphate under corresponding conditions. The distinct increase in myocardial pyruvate content on supplementation with PEP and adenosine triphosphate was most probably due to an adenosine triphosphate-mediated PEP translocation into myocardial cells, with rapid metabolization of translocated PEP into adenosine triphosphate (in the presence of cellular adenosine diphosphate) and pyruvate. The pyruvate and lactate relationship varied, depending on the postischemic conditions. The postischemic myocardial orthophosphate content was stable, with only minor fluctuations. This possibility to supply the postischemic myocardium with substrate for immediate intracellular energy production is of clinical interest and merits further studies.

Adenosine Triphosphate↗

Myocardial high-energy phosphates and function under different postischemic conditions. A study in a paracorporeal rat heart model.

Infusion of phosphoenolpyruvate together with adenosine triphosphate early during reperfusion after ischemia increased the energy content and the left ventricular isovolumic performance in a paracorporeal rat heart model. Excised hearts were subjected to 15 min of complete global ischemia at 37 degrees C before reperfusion. During reperfusion they were either nonworking (empty-beating) or working (performing left ventricular isovolumic work) between 20 and 40 min of reperfusion before freeze-clamping. Early during reperfusion the excised hearts were either supplemented with 144 mumol phosphoenolpyruvate and 0.67 mumol adenosine triphosphate or nonsupplemented (plain saline) administered in a pulsatile arterial blood flow. The supplemented nonworking group showed significantly higher creatine phosphate and adenosine triphosphate contents compared to the nonsupplemented group. However, under postischemic working conditions there were no significant differences in high-energy phosphates between the supplemented and the nonsupplemented groups in spite of significantly better left ventricular isovolumic performance in the supplemented group. Concomitantly the efflux of creatine kinase isoenzyme MB indicating cellular damage was significantly less for this group. The data presented here favor the view of a possible compartmentalized adenosine triphosphate pool with a high metabolic turnover close to the plasma membrane.

Adenosine Diphosphate↗

Adverse effects on the brain in cardiac operations as assessed by biochemical, psychometric, and radiologic methods.

In order to describe subclinical brain injury in conjunction with cardiac operations 94 patients were prospectively studied with three brain injury assessment methods: CSF analyses 24 hours after bypass, psychometry, and computed tomography of the brain. Adenylate kinase (AK), a marker of ischemic brain cell injury, was measured in cerebrospinal fluid (CSF) and in serum. In 13% of the patients, a considerable increase in CSF-AK was seen, in 46% there was a moderate increase, and in 41% no or trivial increase. Psychometry measured as change between preoperative scores in a test battery (SS3) revealed a moderate decrease in intellectual function after operation. There was a significant inverse correlation between CSF-AK and SS3 (r = -0.46, p less than 0.001, r2 = 0.21, n = 71). Computed tomography (CT) of the brain was performed preoperatively and postoperatively in 54 patients. Two of these had cerebral infarctions visible on the CT, despite an essentially normal postoperative state. There was no correlation between indices of brain injury and patient diagnosis and length of perfusion. It is concluded that subclinical brain injury is often seen after cardiac operations. Most often the injury appears trivial and/or reversible, but in a minority of cases there is evidence that the brain injury is irreversible. Factor analysis favors the view that the microembolism theory might no longer be a valid concept in modern cardiopulmonary bypass (CPB). Instead, circumstances in the operative field seem more likely to be important causative factors. This interpretation calls for new principles in the search for an improved cerebral protection during cardiac operations.

Adenylate Kinase↗

Myocardial energy restoration of ischemic damage by administration of phosphoenolpyruvate during reperfusion. A study in a paracorporeal rat heart model.

The myocardial energy restoration of ischemic damage by administration of phosphoenolpyruvate during reperfusion was investigated in a paracorporeal heart model modified in the rat. Excised hearts were subjected to 15 min of complete global ischemia at ischemia at 37 degrees C before pulsatile blood reperfusion for 30 min. One group (n = 7) was supplemented with 67 mumol of phosphoenolpyruvate and 0.67 mumol of adenosine triphosphate dissolved in 10 ml of saline and another with plain saline (nonsupplemented) during reperfusion. All hearts were freeze-clamped after 30 min of reperfusion and subjected to energy content analysis. The adenylate charge potential was 0.91 +/- 0.01 (mean +/- SD) for the supplemented and 0.85 +/- 0.06 (mean +/- SD) for the nonsupplemented group. This difference was significant (p less than 0.02). Concomitantly the outflow of creatine kinase was less for the supplemented group. The translocation of phosphoenolpyruvate into the myocardial cells seems possible by blood supplementation of a lower dose of adenosine triphosphate.

Adenosine Triphosphate↗

Multicentre investigation of myocardial protection with cold cardioplegia.

In order to analyze factors of importance for the efficiency of myocardial protection during open-heart surgery, a study was made of 144 patients undergoing isolated aortic valve replacement with various cardioplegic techniques. The cardioplegia was of Bretschneider type in 54 cases, St Thomas in 31 and Ringer-potassium type in 11 cases. Single or multi-dose blood cardioplegia was used in 11 cases and continuous blood cardioplegia in 30 cases. Local cardiac hypothermia was additionally employed in all patients. The efficiency of myocardial protection was assessed mainly from the incidence of postoperative conduction disturbances, myocardial enzyme release and need for inotropic support. All patients survived the operation. In 20% surgery was followed by transient or persistent disturbance of conduction, in 9% by abnormally increased CK-MB release and in 5% by requirement for inotropic support. Preoperative risk factors such as high age or severe left ventricular (LV) hypertrophy or dysfunction had little influence on the results. Patients in whom aortic stenosis (AS) was dominant in the complex with aortic insufficiency (AS + AI) showed 20-hour postoperative CK-MB enzyme activity twice as high as those with pure aortic insufficiency. The most important factors in myocardial protection were the duration of aortic occlusion and the myocardial temperature during cardioplegia. When the aortic occlusion lasted more than 80 min there was a 32% incidence of conduction disturbances and 20-hour CK-MB activity thrice as high as after shorter occlusion. Patients with mean myocardial temperature below 18 degrees C during cardioplegia invariably had low enzyme activities, which indicated good myocardial protection. The best overall results were obtained in patients operated on during hypothermia at 25-27 degrees C, with single or multi-dose blood cardioplegia and with efficient local cooling of the heart.

Adult↗