Effect of factor XIII on endothelial barrier function.

The effect of factor XIII on endothelial barrier function was studied in a model of cultured monolayers of porcine aortic endothelial cells and saline-perfused rat hearts. The thrombin-activated plasma factor XIII (1 U/ml) reduced albumin permeability of endothelial monolayers within 20 min by 30 +/- 7% (basal value of 5.9 +/- 0.4 x 10(-6) cm/s), whereas the nonactivated plasma factor XIII had no effect. Reduction of permeability to the same extent, i.e., by 34 +/- 9% could be obtained with the thrombin-activated A subunit of factor XIII (1 U/ml), whereas the iodoacetamide-inactivated A subunit as well as the B subunit had no effect on permeability. Endothelial monolayers exposed to the activated factor XIII A exhibited immunoreactive deposition of itself at interfaces of adjacent cells; however, these were not found on exposure to nonactivated factor XIII A or factor XIII B. Hyperpermeability induced by metabolic inhibition (1 mM potassium cyanide plus 1 mM 2-deoxy-D-glucose) was prevented in the presence of the activated factor XIII A. Likewise, the increase in myocardial water content in ischemic-reperfused rat hearts was prevented in its presence. This study shows that activated factor XIII reduces endothelial permeability. It can prevent the loss of endothelial barrier function under conditions of energy depletion. Its effect seems related to a modification of the paracellular passageways in endothelial monolayers.

Expression of sodium pump isoforms and other sodium or calcium ion transporters in the heart of hypertensive patients.

The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the enzyme responsible for the maintenance of membrane potential, for the function of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased contractility of the heart muscle and increased blood pressure, we were interested in whether there is a correlation between hypertension and expression of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)- and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and normotensive patients who were undergoing cardiac surgery. After reverse transcription and subsequent amplification of ion transporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-(32)P]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that the alphal subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)-exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is possible that the observed changes in mRNA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+) metabolism in the tissues of hypertensive patients or reflect defects directly involved in the cause of hypertension. The expression of mRNA for all other transporters investigated was unaltered.

Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction.

The Del allele of the apolipoprotein B (apoB) signal peptide (SP) insertion/deletion (Ins/Del) polymorphism has been shown to be associated with elevated plasma levels of apoB, cholesterol and low density lipoprotein. It was the aim of the present study to analyse the relation of this gene variation to the risk of coronary artery disease (CAD) and of myocardial infarction (MI) in a population of 2259 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. ApoB SP DelDel genotypes had significantly higher apoB plasma concentrations than InsIns homozygotes (P = 0.0001) and InsDel heterozygotes (P = 0.002); however, the apoB plasma levels of InsIns and InsDel genotypes were essentially the same (P = 0.54). Similar observations were made with respect to ApoB SP genotype-dependent cholesterol plasma concentrations. Since the apoB plasma level was not only associated with the apoB SP Ins/Del gene variation but also to the extent of coronary artery disease (P <0.0001), individuals with an InsIns genotype and without CAD had the lowest and subjects with a DelDel genotype and triple vessel disease the highest apoB plasma levels (P <0.0001). An association of the apoB SP Ins/Del gene variation with CAD was not detected, neither in the total population nor in low risk groups. In contrast, the gene variation was associated with MI (P <0.05). An Odds ratio of 1.18 (95% CI, 1.01-1.39) associated with the Del allele was detected in the total sample (P <0.02). In a subpopulation of individuals with low plasma triglyceride levels ( <154 mg/dl; mean value) and an DD genotype of the angiotensin I-converting enzyme insertion/deletion gene polymorphism an Odds ratio of 2.01 (1.42-3.05) was calculated (P <0.001). The present study presents evidence for a statistically significant difference in the development of MI between genotype classes of the apoB SP Ins/Del gene polymorphism.

ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals.

BACKGROUND: Presence of the D allele or homozygosity for the deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In 2267 male Caucasians the relation of the ACE I/D gene polymorphism to CAD and MI were investigated. An association of the D allele to CAD was detected in younger subjects (e.g. < 61.7 years, mean value), but not in older patients (e.g. > or = 61.7 years). Additional exclusion of individuals with other cardiovascular risk factors (e.g. high BMI) produced an even stronger association of the D allele to CAD. In contrast, a relation of this polymorphism to non-fatal MI was only observed in older subjects; additional limitation to individuals without cardiovascular risk factors (e.g. BMI and/or diabetes) yielded a further enhancement of this association to MI. In younger subjects (e.g. < 61.7 years) the gene polymorphism was not related to non-fatal MI even after exclusion of additional risk factors. CONCLUSIONS: The present large case-control study strengthens the assumption of an association of the ACE D allele with the risk of ischemic heart disease.

Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis.

BACKGROUND: The relations of the angiotensinogen (AGT) T174M and M235T gene polymorphisms to the risk of coronary heart disease (CHD) have been investigated in only a few studies with conflicting results. RESULTS: Therefore, we analysed the relationship of the AGT gene polymorphisms to the presence and extent of CHD in 2250 male Caucasians whose coronary anatomy was defined by means of coronary angiography. The relative frequencies of the T and M alleles of the T174M and of the M235T gene variation did not significantly differ between patients without or with single-, double- or triple-vessel disease and between subjects without or with myocardial infarction (MI). In contrast the mean CHD score--defined by Gensini--was higher within MM homozygotes of the T174M gene variation than within TT genotypes; TM subjects had intermediate values. In M235T genotypes, mean CHD scores were similar in the total sample and in older individuals (> or = 62 years), whereas in younger individuals (< 62 years) a higher CHD score was found within AGT 235 T allele carriers than within MM homozygotes. In younger individuals with high apoAI plasma levels, the mean CHD score was clearly higher within TT homozygotes of the M235T gene variation than within MM genotypes; MT subjects had intermediate values. An interaction between both angiotensinogen gene polymorphisms on the extent of CHD or on the risk of non-fatal MI were not observed when the M allele of AGT T174M was combined either with the T allele or the TT genotype of M235T. CONCLUSIONS: The present study strengthens the hypothesis of an association of both angiotensinogen gene polymorphisms with the extent of coronary heart disease.

The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high risk for this disease.

BACKGROUND: Disturbances in fibrinolytic activity, such as increase in plasminogen activator inhibitor (PAI) activity, have been linked with an increased risk for coronary artery disease (CAD) and myocardial infarction (MI). Since 4G4G homozygotes of an insertion/deletion (4G/5G) gene variation in the promoter of PAI-I have been shown to have increased levels of PAI-I, we analysed the relation of this gene polymorphism to CAD and MI in a population of 2565 participants who underwent coronary angiography for diagnostic purposes. RESULTS: In the total sample, the PAI-I 4G/4G genotype was associated with the presence, but not with the extent of CAD. However, in a subgroup of former and present smokers (n = 1782) or of individuals with a BMI above the mean value of 26.9 kg x m(-2) (n = 1269), the PAI-I 4G4G genotype was not only associated with the presence, but also with the extent of CAD, defined either by the number of diseased vessels or by the CHD score according to Gensini. This observation also applied to other high-risk groups of individuals with high BMI and hypertension (n = 869), of subjects with high fibrinogen plasma levels (>3.53 g x l(-1), mean value) and hypertension (n = 599) and of former and present smokers with high fibrinogen and hypertension (n = 452). An association of the gene variation with MI was not detected. CONCLUSIONS: The present data indicate that the 4G/4G genotype of the PAI-I gene polymorphism is an independent risk factor for coronary artery disease and that the additional presence of major cardiovascular risk factors accelerates the risk for this disease.

The factor II G20210A and factor V G1691A gene transitions and coronary heart disease.

BACKGROUND: G to A transitions at nucleotide position 20210 of the factor II (Fll) gene and at 1691 of the factor V (FV) gene have been shown to be associated with an increased risk of venous thrombosis. Since it is still unclear whether both gene variations are also related to an increased risk of coronary heart disease (CHD), we studied the relation of both gene variations to coronary artery disease (CAD) and myocardial infarction (MI) in a sample of 2210 male individuals whose coronary anatomy were defined by coronary angiography. RESULTS: In the total sample, the FII G20210A gene variation was not associated with the presence or the extent of CAD, the latter defined either by the degree of vessel disease or by a CHD score according to Gensini. However, individuals with unfavourable lipid profiles showed pronounced differences in CHD scores between GA heterozygotes and GG homozygotes: this observation applied in particular to younger patients (<62 years; mean age of total sample) who simultaneously had low apoAI/apoB ratios (< 1.19, mean value) and high Lp(a) plasma levels (>28 mg/dl; mean value). In addition, in subjects without acetylsalicylic acid treatment GA heterozygotes had clearly higher CHD scores than AA genotypes. Further restriction to smokers, to subjects with high fibrinogen plasma levels (>3.47 g/l; mean value) or to patients with high glucose concentrations (>112 mg/dl; mean value) tended to increase the difference in CHD score between FII G20210A genotypes. An association of the FII G20210A gene variation with non-fatal MI was not observed. In the total sample and in high and low risk subpopulations, an association of the FV G1691A gene variation was not detected neither with presence and extent of CAD or with nonfatal MI. CONCLUSION: The importance of the factor II G20210A gene variation for CHD may be restricted to individuals with major cardiovascular risk factors. In addition, the present study did not strengthen the hypothesis of the factor V G 1691 A transition as a risk factor of coronary heart disease neither in the total sample nor in subgroups of individuals who were at high or low risk of CHD.

Association of the platelet glycoprotein IIIa PlA1/A2 gene polymorphism to coronary artery disease but not to nonfatal myocardial infarction in low risk patients.

BACKGROUND: The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation. In a small case-control study, evidence has been presented that the PlA2 allele of the platelet glycoprotein GPIIIa PlA/A2 gene polymorphism might be an independent risk factor for acute myocardial infarction (MI). METHODS AND RESULTS: We explored the association of the PlA1A2 to the severity of coronary artery disease (CAD), as assessed angiographically in 2252 male individuals, and to myocardial infarction (MI). The severity of coronary heart disease (CHD) was also estimated by calculating a CHD score according to Gensini. The PlA genotype was determined by allele specific restriction digestion. Relation of the PlA2 allele to CAD: In the total population, the frequency of the PlA2 allele was not associated to the presence or to the extent of CAD. Also the CHD scores of PlA1/PlA2 genotypes were essentially the same. However, after exclusion of individuals with high BMI (> or =26.9 kg/m2) and/or low apoAI (< 1.43 g/l) PlA2PlA2 carriers had clearly higher CHD scores than PlA1PlA1 genotypes: PlA1PlA2 heterozygotes had intermediate values (p <0.05). After division of the study population into one group of individuals without any angiographic signs of CAD (CHD score = 0) and into another group of patients with severe CAD (CHD score (> or = 120), a strong association of the PlA2 allele with severe CAD was also found in the same low risk groups: e.g. exclusion of persons with high BMI and low apoAI resulted in an Odds ratio of 5.37 (1.46-19.7) (p <0.02). Relation of the PlA2 allele to MI: No association was found between PlA1/PlA2 genotypes and risk of MI neither in the total population nor in low risk subgroups. CONCLUSIONS: Whereas no difference in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the PlA2 allele is associated with CHD in low risk patients.

Positive association of the beta fibrinogen H1/H2 gene variation to basal fibrinogen levels and to the increase in fibrinogen concentration during acute phase reaction but not to coronary artery disease and myocardial infarction.

BACKGROUND: Fibrinogen has been demonstrated to be an independent risk factor of cardiovascular disease. The absence of the HaeIII cutting site (H2 allele) of an H1/H2 gene variation in the promoter region of the beta fibrinogen gene was associated with increased levels of fibrinogen. METHODS AND RESULTS: In the present study, the effects of the H1/H2 gene variation not only on plasma fibrinogen concentrations but also on coronary artery disease (CAD) and myocardial infarction (MI) were investigated in 923 individuals who underwent coronary angiography for diagnostic purposes. Relation of the H1/H2 genotype to fibrinogen plasma levels: A strong association was observed between the H1/H2 gene variation and fibrinogen levels. The differences in fibrinogen plasma levels between H2H2 and H1H1 homozygotes were almost threefold more pronounced within subjects with clinical chemical signs of an acute phase reaction (CRP > or = 7.5 mg/l) than within a subgroup of subjects without these signs (CRP < 7.5 mg/l) (median of CRP distribution: 7.5 mg/l). In 207 patients who underwent aortocoronary bypass surgery plasma fibrinogen levels were almost identical directly after surgery. Two days after operation fibrinogen increased to clearly higher levels in H2H2 homozygotes than in H1H2 and H1H1 genotypes, whereas almost the same maximal increases in fibrinogen concentrations were reached 3-4 days after surgery in all individuals. Relation of the H1/H2 genotype to CAD and MI. Whereas in the total population the plasma fibrinogen concentrations were strongly associated with smoking, CAD and MI, an association of the H1/H2 gene variation to CAD and MI was not detected. However, mean age at first MI of H2H2 individuals (62.9 years) was clearly higher than of H1H2 genotypes (56.9 years) and of H1H1 subjects (56.4 years). In addition, in a subgroup of individuals with a higher risk of MI by either high apoB and/or low apoA1 plasma levels the portion of MI patients was clearly smaller within H2H2 homozygotes than within H1H2 or H1H1 genotypes, although-also in these high risk groups-mean age at first MI of H2H2 individuals were higher than of the other two genotypes. CONCLUSIONS: Obviously, the H2 allele of the fibrinogen H1/H2 genotype does not only influence basal fibrinogen concentrations, but particularly also the extent of fibrinogen level increase during acute phase reaction. Whereas the fibrinogen plasma level is positively associated with coronary artery disease and myocardial infarction, the H2 allele-although exhibiting an association with elevated fibrinogen levels-was not positively associated with CAD and MI.

Intraoperative evaluation of the functional significance of coronary collateral vessels in patients with coronary artery disease.

Coronary hemodynamics were studied intraoperatively in 65 patients undergoing aortocoronary bypass grafting. Poststenotic coronary pressure and graft flow hyperemia were measured. Patients without coronary collateral vessels on arteriography (class A) were compared with patients with collateral vessels (class B). Patients in class A were grouped according to the angiographically determined degree of coronary stenosis. Eight of these patients with moderate coronary stenosis underwent intraoperative studies with transient complete coronary occlusion and were classified in the "acute" occlusion group. In class B all patients had complete coronary occlusion with good retrograde filling of the distal segment. In class A patients there was good correlation between the degree of stenosis and poststenotic pressure or hyperemic response. Stenosis had to be at least 80 percent before it produced a significant pressure gradient or graft flow hyperemia. In class B patients (those with complete "chronic" coronary occlusion), poststenotic pressure was significantly greater than in the class A patients with "acute" occlusion, significantly less than in the class A groups with 71 to 80 percent and 81 to 90% stenosis but not significantly different from values in the class A group with 91 to 99 percent stenosis. The hyperemic response was significantly less than in the "acute" occlusion group of class A, significantly greater than in the class A groups with 71 to 80 percent and 81 to 90 percent stenosis, but not significantly different from values in the class A group with 91 to 99 percent stenosis. It is concluded that (1) under basal conditions a coronary stenosis must be at least 80 percent to be hemodynamically significant, and (2) well developed collateral vessels produce in a completely occluded coronary artery hemodynamic changes that simulate those of a 90 percent coronary stenosis without collateral vessels.

Incidence and pathogenesis of late aneurysms after patch graft aortoplasty for coarctation.

From 1957 to 1984 direct and indirect isthmoplasty as described by Vossschulte has been the method of choice for surgical therapy of coarctation of the aorta in our hospital. A total of 317 patients have been so treated, 54 of whom were less than 12 months old at operation. The hospital mortality in this group was 15% and the mortality in patients older than 1 year was 3%. The early results were encouraging, but during follow-up an increasing number of postoperative aneurysms have been detected. During reinvestigation an aneurysm was diagnosed in 18 cases. Therefore, we have studied the cause of these aneurysms. To this point reoperation has been performed in 15 patients having late aneurysms. Extensive resection of a fibrous membrane of the aortic isthmus at the first intervention seems to be an essential predisposing factor for development of aneurysms. Microscopic examination of the aneurysmal wall revealed degeneration of the media in more than half of the patients. From our experience we conclude that the posterior fibrous ridge should no longer be excised and the Vossschulte operative technique should be viewed more critically.

Pediatric heart transplantation for congenital heart disease and cardiomyopathy.

Orthotopic heart transplantation has become an accepted therapy for adult patients with end-stage heart disease. In newborns and infants, this procedure is still controversial because of the unknown long-term results and the lack of donor organs. Since March 1988, we have performed orthotopic heart transplantation in 11 infants and children with hypoplastic left heart syndrome (n = 6), cardiomyopathy (n = 4), or congenital endocardial fibroelastosis (n = 1). The smallest infant was 3 days old and weighed 2,650 g. Four of 15 potential donors had to be refused for various medical reasons, and 4 were transferred to our hospital for organ retrieval. Seven hearts were procured remotely. We accepted weight mismatches up to 105% between donor and recipient. There were three perioperative deaths, two in patients 5 and 17 days old with hypoplastic left heart syndrome and 1 in a 2-year-old patient with a dilated cardiomyopathy. All 3 patients had drug-resistant right heart failure. A 2-year-old girl with a dilated cardiomyopathy died 2 months after transplantation owing to severe pulmonary embolism originating from the superior vena cava. The remaining 7 patients are alive and well between 1 month and 31 months after transplantation. Angiographic follow-up has not revealed signs of graft atherosclerosis at 2 years.

Effects of prostacyclin during cardiopulmonary bypass in men on plasma levels of beta-thromboglobulin, platelet factor 4, thromboxane B2, 6-keto-prostaglandin F1 alpha and heparin.

A randomized double-blind study was carried out on 40 male patients requiring aorto-coronary bypass surgery. 20 patients received a constant dose of 8 ng kg-1 min-1 of prostacyclin (PGI2), beginning two minutes before extracorporeal circulation (ECC) and ending together with ECC. Compared to the placebo-treated patient group (n = 20), PGI2-treatment significantly reduced the ECC-induced release of platelet alpha-granule proteins, beta-thromboglobulin (1178 ng/ml vs. 1926 ng/ml) and platelet factor 4 (837 ng/ml vs. 1245 ng/ml) into plasma (mean of max. values). Furthermore the decrease of platelet counts during ECC was less pronounced in PGI2-treated patients. Application of PGI2 had no effect on the increase in thromboxane B2 (TxB2) plasma levels, which amounted to 0.6 ng/ml at the end of ECC. PGI2-treatment resulted in significantly elevated plasma concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (2.1 ng/ml) throughout the infusion off prostacyclin. 6-keto-PGF1 alpha plasma levels increased up to 1.2 ng/ml in the control group patients, indicating a stimulation of endogenous PGI2 formation during ECC.

Prostacyclin in aortocoronary bypass surgery: a double-blind, placebo-controlled study.

In a double-blind, placebo-controlled trial of 40 patients requiring aortocoronary vene transplant surgery, prostacyclin (PGI2) was infused in a dose of 8 ng/kg/min throughout cardiopulmonary bypass. When compared with the placebo-group, the patients treated with PGI2 were found to have significantly higher platelet counts 60(2) and 90 minutes after onset of extra-corporeal circulation (EC). Although this platelet preservation by PGI2 was accompanied by less degranulation of alpha-granula, total antithrombin III (AT III) as well as active AT III and factor Xa inhibitory activity did show comparable results in both treatment groups. In the early phase of EC coagulation factors (fibrinogen, prothrombin and factor VII) exhibited a trend in favour of higher plasma levels in the PGI2-treated group. The same results were found for plasminogen. F VIII-related antigen and complement factors (C3, C4, C3 activator) did not show any difference between the two treatment groups. Bleeding times, blood loss and renal function also did not exhibit any significant differences between the two groups of patients. Except for one control (60 minutes after onset of EC) hemodynamic parameters were not significantly different between the two patient groups. Whether the trend in favour of a lower mortality in PGI2-treated patients can be confirmed, will be up to further studies with greater numbers of patients.

Endothelin-1 and vasopressin plasma levels are not associated with the insertion/deletion polymorphism of the human angiotensin I-converting enzyme gene in patients with coronary artery disease.

The objective was to investigate whether the renin-angiotensin (RA) system and related peptides endothelin-1 (ET-1) and vasopressin (VP) influence the development of coronary artery disease (CAD). Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been associated with the risk of CAD. The ACE I/D polymorphism determines ACE activity, but plasma levels of other RA system components remain unchanged. However, ET-1 and VP production could be increased by RA system-dependent stimulation, continually promoted by paracrine stimulation and sustained by neointimal growth. ET-1 and VP have not been associated with the ACE I/D polymorphism so far. The present study investigated the association of the ACE I/D polymorphism with plasma concentrations of ET-1 and VP, as well as with renin, angiotensin-II (AT-II) and ACE activity in 98 Caucasian individuals with CAD. ACE I/D polymorphism showed no association with plasma levels of VP, ET-1, AT-II or renin. These parameters were also not associated taking into consideration different patient variables, such as diabetes mellitus, hypertension or severity of CAD. Only plasma ACE activity was associated with the D allele. In conclusion, the ACE I/D polymorphism could not be related to plasma concentrations of VP, ET-1, renin or AT-II, but as previously demonstrated, it could only be related to ACE activity in patients with CAD. Differences in ACE activity between ACE I/D genotype subgroups are probably compensated within the RA system itself or within non-ACE pathways, so that plasma concentrations of the related peptides ET-1 and VP remain unaffected.

Influence of 4 different membrane oxygenators on inflammation-like processes during extracorporeal circulation with pulsatile and non-pulsatile flow.

The influence of four different membrane oxygenators (HF 4000, BOS-CM 50, CML 2, Maxima) on leucocyte count, concentrations of PMN-elastase, clotting factor XII, AT-III, C1-INH, alpha 2-antiplasmin and C3a was registered before, during and after CPB with pulsatile and nonpulsatile flow in 80 male patients aged between 36 and 67 years. With all systems tested, there was a drop in the concentrations of clotting factor XII, AT-III, C1-INH and alpha 2-antiplasmin in the early extracorporeal circulation (ECC) phase, exceeding the average hematocrit reduction accounted for by dilution. This drop was the least distinct with CML 2 systems, both with pulsatile and nonpulsatile perfusion, indicating system-inherent influences. Leucocyte cound and PMN-elastase concentration rose significantly during ECC irrespective of oxygenator tested of flow type applied. The rise in leucocyte count even continued for about 4 h after ECC. During the first 40 min of ECC, these changes were paralleled by a significant rise in C3a concentration, suggesting complement activation as a main cause for PMN activation. However, there is reason to suppose involvement of further mechanisms operating in PMN activation, since the elevated C3a-concentrations began to fall off while leucocyte count and PMN-elastase concentrations were still increasing.

Myocardial protection of hypertrophied hearts by administration of cardioplegia according to regional myocardial temperature.

Hypertrophied hearts are known to be extremely vulnerable to ischemia. During cardioplegic arrest different regional myocardial temperature are known to occur. We investigated myocardial protection in 61 patients with aortic valve disease undergoing aortic valve replacement. Three different cardioplegic solutions were used. Regional myocardial temperature was continuously controlled and adjusted to a temperature of not more than 15 degrees C by intermittend infusion of cardioplegia. Before, after heart arrest and after 10 minutes of reperfusion we did myocardial biopsies and determined high energy phosphates and lactate. From our results we conclude that three cardioplegic solutions were able to protect hypertrophied hearts adequate during an ischemic period of 60 minutes if the regional myocardial temperature does not increase above 15 degrees C.

Ultrastructure of the human myocardium after intermittent ischemia compared to cardioplegia.

A lot of reports informed about the detrimental effects of intermittent ischemia nevertheless this method is still used during coronary surgery. We investigated the myocardial protection due to cardioplegic arrest compared to intermittent ischemia in 120 patients undergoing coronary surgery. In all patients we took myocardial biopsies from the left ventricle before and after ischemia. Electron microscopic studies of all biopsies were performed and the degree of ultrastructural alteration was determined. The ischemic period in the cardioplegic group was 61 +/- 15 minutes and in the group with intermittent ischemia the total ischemic time was 45 +/- 21 minutes. After ischemia the myocardium showed most time only damage of moderate or light degree, while after intermittent ischemia the most biopsies showed severe ultrastructural damage. From our results we conclude, that intermittent ischemia is unable to protect the myocardium in a sufficient amount and should therefore no longer be used as a method of myocardial protection.

Heart valve replacement with the new all-pyrolytic bi-leaflet St. Jude medical prosthesis.

Since February 1978, seventy-nine St. Jude medical prostheses have been implanted in seventy-two patients with an overall mortality of 8.5%. Clinical, hemodynamic and hematological findings are presented. Twenty-two patients have been catheterized postoperatively, and findings are presented. In vitro comparisons have made between the St. Jude and other prostheses.

Experimental studies of the influence of priming solutions on the systemic activation of complement during cardiopulmonary bypass: comparison between the use of albumin, hydroxyethyl starch and HWA-138.

Cardiopulmonary bypass surgery may be complicated by a systemic inflammatory reaction, which has been ascribed to activation of complement. For such activation, the choice of priming solution for the heart-lung machine may be of importance. The peripheral blood of three groups of eight donors was exposed to albumin, hydroxyethyl starch (HES) or to HWA-138 (pentoxifylline analogue) in addition to the priming solutions. The study confirmed that activation of complement is a consistent phenomenon during cardiopulmonary bypass surgery. The concentration of the C3 activation product C3a in the plasma was significantly increased after simulated extracorporeal circulation. However there were no differences within the increase of C3a concentrations between the various priming solutions.