Hilchen T. Sommerschild

Preconditioning - endogenous defence mechanisms of the heart.

The term ‘preconditioning’ refers to the paradoxical phenomenon that pretreatment with a potential noxious stress‐stimulus can increase cellular tolerance to subsequent noxious stress‐stimuli. This was first described in an experimental model in dogs in which short‐lasting periods of myocardial ischemia resulted in reduced infarction during a subsequent long‐lasting coronary artery occlusion. Similar observations have also been made in other species and in other organs. During the last few years, the term preconditioning has been expanded to include pretreatment with other physical stress‐stimuli or pharmacological agents that can increase cellular resistance to injury. The phenomenon probably represents a general adaptive response to cellular stress, but mechanisms involved are not fully clarified.

Microembolization in pigs: effects on coronary blood flow and myocardial ischemic tolerance.

Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 × 106, 15 μm in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 ± 1.5 (SE) + (5.8 ± 0.7 × 10-7 × number of injected microspheres). Because injection of 40 × 106 microspheres induced a long-lasting hyperemic response, which could be blocked by 8- p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 × 106microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 ± 3% of area at risk in control animals to 84 ± 6% ( P< 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.Coronary microembolization has been reported to increase coronary blood flow (CBF) through adenosine release. Because adenosine may increase ischemic tolerance against infarction, we tested the hypothesis that myocardial microembolization, a common finding in patients with ischemic heart disease, induces cardioprotection. Additionally, because the use of microspheres is a common tool to measure tissue perfusion, the effects of small amounts of microspheres on CBF were examined. Using anesthetized pigs, we measured CBF with a transit time flow probe on the left anterior descending coronary artery (LAD). In six pigs the relationship between the amount of injected microspheres (0-40 x 10(6), 15 micrometer in diameter, left atrial injections) and the effect on CBF was examined. Coronary hyperemia occurred, which was linearly related to the amount of microspheres injected: maximal increase in CBF (%) = 2.8 +/- 1.5 (SE) + (5.8 +/- 0.7 x 10(-7) x number of injected microspheres). Because injection of 40 x 10(6) microspheres induced a long-lasting hyperemic response, which could be blocked by 8-p-sulfophenyl theophylline, ischemic tolerance was examined in five other pigs after two injections, each of 40 x 10(6) microspheres, at a 30-min interval. Six control pigs had no injections. Ischemic tolerance was evaluated by measuring infarct size (tetrazolium stain) as the percentage of area at risk (fluorescent particles) after 45 min of LAD occlusion followed by 2 h of reperfusion. Pretreatment by microspheres increased infarct size from 60 +/- 3% of area at risk in control animals to 84 +/- 6% (P < 0.05). The injection of microspheres induced a significant hyperemic flow response without causing necrosis by itself. We conclude that microembolization, evoking coronary hyperemia, does not improve but reduces myocardial ischemic tolerance against infarction in pigs.

Proarrhythmic effects of ischemic preconditioning in anesthetized pigs.

Conflicting data exist on how ischemic preconditioning affects the incidence of arrhythmias during ischemia. The present study was, therefore, performed to clarify if ischemic preconditioning alters the incidence of arrhythmias during the early phase of ischemia in pigs.Twenty-four pigs (23–36.5 kg) in pentobarbital anesthesia were preconditioned by a 10 min LAD-occlusion and 30 min reperfusion prior to a second 10 min occlusion. The first occlusion served as the preconditioning ischemic period, and the second occlusion as the test ischemic period. To verify that the preconditioning protocol induced protection, infarct size was assessed in an additional nine pigs.The arrhythmic index (arrhythmic beats/min) increased from 12±3 during the first occlusion to 38±8 during the second occlusion (P<0.05). Four pigs (17%) fibrillated during the first ischemic period, while 10 pigs (42%) fibrillated during the second ischemic period (P<0.05). All pigs that fibrillated during the first occlusion also fibrillated during the second occlusion. Mean heart rate was 108±4 beats/min before the first occlusion and increased to 113±4 beats/min before the second occlusion (P<0.001). There was a positive correlation between heart rate before the second occlusion and occurrence of fibrillation during this occlusion (rs=0.42; P<0.05). The preconditioning protocol reduced infarct size, after a subsequent 45 min ischemic period followed by two hours of reperfusion, from 58±3% of area at risk to 40±5% (P<0.05).In conclusion, our data show that ischemic preconditioning increases both the arrhythmic index and the incidence of ventricular fibrillation during the early phase of a subsequent ischemic period.

Importance of Endogenous Adenosine During Ischemia and Reperfusion in Neonatal Porcine Hearts

BACKGROUND Adenosine has several potentially cardioprotective effects. We hypothesized that the effects of endogenous adenosine vary with degree of ischemia and that elevating endogenous levels is protective. METHODS AND RESULTS Isolated blood-perfused piglet hearts underwent 120 minutes of low-flow ischemia (10% flow) or 90 minutes of zero-flow ischemia, all with 60 minutes of reperfusion. Hearts were treated with either saline, the adenosine receptor blocker 8-sulfophenyltheophylline (8SPT, 300 micromol x L(-1)), or the nucleoside transport inhibitor draflazine (1 micromol x L(-1)). In separate groups, biopsies were obtained before and at the end of ischemia. Compared with saline, 8SPT did not significantly alter functional recovery in either protocol. Draflazine significantly improved percent recovery of left ventricular systolic pressure both in the low-flow protocol (92+/-3% versus 75+/-2% [saline] and 73+/-3% [8SPT], P<.001 for both) and in the zero-flow protocol (76+/-3% versus 59+/-4% [saline] and 46+/-9% [8SPT], P<.05 for both). In the zero-flow protocol, draflazine also significantly reduced ischemic contracture and release of creatine kinase. Tissue adenosine at the end of ischemia was elevated by draflazine compared with saline-treated hearts: after low-flow ischemia to 0.10+/-0.05 versus 0.00+/-0.00 micromol x g(-1) dry wt (P<.05) and after zero-flow ischemia to 1.73+/-0.82 versus 0.15+/-0.03 micromol x g(-1) dry wt (P<.05). CONCLUSIONS In neonatal porcine hearts, endogenous adenosine produced during ischemia does not influence ischemic injury or functional recovery. Elevating endogenous adenosine by draflazine elicits cardioprotection in both low-flow and zero-flow conditions.

Prevention in child psychiatry

Abstract Prevention in child psychiatry may be divided into two different areas: Promotion of mental health and prevention of psychiatric illness. In promotion of mental health the target is the total population and one has to deal with values within the sociocultural frame of reference. Research pilot projects have been carried out by the establishment of different parents groups. The intention of this group‐work has been of a cultural ‐not an educational ‐ nature. We have tried to create a replica of the lost possibility of cultural transference of skills and norms in caring and upbringing. In prevention of psychiatric illness the work must be based on epidemiology and the risk groups are the specific target. Research projects in prevention have been rather limited, but we may draw two con clusions: To identify the risk children has not been the problem ‐ the interventions must be rather comprehensive for counteracting the risk factors, rendering them harmless.