Serial changes of soluble endothelin-1 levels during myocardial ischaemia-reperfusion. Effects of magnesium, diltiazem and a novel MAC-1 inhibitor.

The key role of endothelin-1 (ET-1) has been recognised in patients with ischaemic heart disease. However, the serial changes of ET-1 during both brief and prolonged ischaemia-reperfusion are poorly known. Serial changes of plasma ET-1 were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem and a MAC-1 inhibitor on the plasma ET-1 were elucidated. Forty-nine swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. ET-1 plasma concentration was measured by ELISA at prespecified time points. The occlusion was associated with a decline of ET-1 followed by a significant increase during the reperfusion. Mg as well as diltiazem similarly affected the plasma ET-1 by reducing ET-1 release during the first hour of the reperfusion period. MAC-1 inhibition was also associated with decreases of ET-1. Ability of Mg, diltiazem and leumedins to decrease the ET-1 plasma level may have direct clinical implications for the use of these agents in patients with coronary artery disease.

Plasma fibronectin during myocardial ischemia-reperfusion: effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

The important role of fibronectin (Fn) has been recognized in patients with ischemic heart disease. However, serial changes of Fn during both brief and prolonged ischemia-reperfusion are poorly known. Plasma Fn was measured during acute myocardial infarction (AMI) and myocardial stunning (MS), and in the absence of myocardial injury. The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on the level of Fn were elucidated. Forty-nine swine underwent prolonged (50 min) or brief (8 min) coronary artery occlusion followed by reperfusion, while six control animals were free of ischemia. During the AMI experiments, plasma Fn underwent a significant progressive increase. Mg or diltiazem similarly affects the plasma Fn, reducing its release during the entire reperfusion period, and did not influence the plasma Fn in the absence of myocardial injury. Contrarily, Mac-1 inhibition resulted in the Fn elevation in controls, and during the occlusion phase, with no significant effect during reperfusion. There were no changes in the plasma Fn during MS, while inhibition of Mac-1 was associated with the significant increase of Fn during ischemia-reperfusion. Ability of Mg, diltiazem, and leumedins to modulate plasma Fn level may have direct clinical implications for the use of these agents in patients with coronary artery disease.

Deployment of a previously embolized, unexpanded, and disarticulated Palmaz-Schatz stent.

Stent embolization is a rare but acknowledged complication of placement of disarticulated (half) Palmaz-Schatz stents. We report a case in which we diagnosed a previously unrecognized, embolized, undeployed half-stent in the distal LAD, causing slow flow, and then deployed the stent where it lay, resulting in improved flow. The literature on treatment of coronary stent embolization and on cutting and preparing half-stents for deployment is discussed.

Effects of intracoronary diltiazem on certain hemostatic parameters during acute myocardial infarction in swine.

Controversy currently exists regarding the use of diltiazem in the treatment of acute myocardial infarction (AMI). due to conflicting results from clinical trials and animal studies. The purpose of this project was to evaluate the changes in the hemostatic profile during AMI following low dose intracoronary diltiazem infusion. Fourteen Yorkshire swine underwent thoracotomy and 50 min LAD occlusion, followed by 3 h of reperfusion. The first group (n = 8) received 2.5 mg of diltiazem intracoronary at a rate of 5.6 micrograms kg min-1 at the onset of reperfusion. The second group (n = 6) received 0.9% saline intracoronary at the onset of reperfusion and served as the control. The dynamics of plasma antithrombin-III (AT-III), Protein C, total Protein S, fibronectin, endothelin-1 (ET-1), and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1a) were determined at baseline, then twice during occlusion and finally three times during reperfusion. Diltiazem infusion resulted in diminished ET-1 (34.5%), fibronectin (23.2%), and TxB2 (35.6%); and elevated Protein C (29.3%) when compared with controls. We conclude that intracoronary diltiazem favorable influences hemostasis during AMI in swine. The cardioprotective effects of diltiazem during AMI may be related to the improved hemostatic profile and the reduced incidence of thrombotic complications in such patients.

Bolus magnesium infusion in humans is associated with predominantly unfavourable changes in platelet aggregation and certain haemostatic factors.

UNLABELLED: The purpose of this study was an attempt to extrapolate favorable observations on the effects of magnesium on platelets and haemostasis from animal models to humans. Intravenous magnesium in the treatment of acute myocardial infarction has been tested in several large clinical trials and remains controversial. The mechanism for the cardioprotective properties of magnesium is unknown. Based on experimental studies, several different hypotheses have been advanced to explain the benefits of magnesium including it's effects on platelets and haemostasis. However, few studies have analysed such a relationship in humans. This project was designed to assess the effect of bolus magnesium infusion on ex vivo platelet aggregation and certain haemostatic parameters in healthy volunteers. One gram of magnesium was diluted in 50 ml of D5W and infused over a period of 15 min. The changes of platelet aggregability, plasma antithrombin-III, Protein C, total Protein S, fibronectin, endothelin-1, as well as the metabolites of thromboxane and prostacyclin were determined prior to and immediately after magnesium infusion. RESULTS: Serum magnesium concentration increased from 2.10 +/- 0.08 at baseline to 3.12 +/- 0.13 mg dl-1 (P = 0.0002) post-infusion. Magnesium infusion was associated with a significant elevation in ADP (+19.3%); ristocetin (+13.6%); and collagen-induced platelet aggregation (+14.2%); an increase in plasma antithrombin-III (+10.3%) and thromboxane (+49.4%) when compared to pre-infusion levels. Against this, total Protein S (-20.7%), Protein C (-11.2%) and ET-1 (-26.3%) plasma concentrations were markedly decreased. There were no significant differences in plasma fibronectin and prostacyclin levels. Contrary to expectations, magnesium infusion in human volunteers is associated with platelet activation and mostly small unfavourable changes in certain haemostatic factors. However, the observed changes were small and for the most part remained within the normal physiologic range.

Short-term low dose intracoronary diltiazem administered at the onset of reperfusion reduces myocardial infarct size.

BACKGROUND: Currently, controversy exists regarding the use of calcium-channel blockers in the treatment of acute myocardial infarction (AMI), due to apparent conflicting results from clinical trials and animal models. One hypothesis to explain such a discrepancy proposes that the timing and duration of drug administration might influence its cardioprotective effect. Pretreatment with calcium-channel blockers or their administration during coronary artery occlusion is associated with the diminished infarct size in animal models. While verapamil failed to reduce infarct size when the drug was given at the onset of reperfusion, similar effects of low dose diltiazem are not known. METHODS AND RESULTS: This experiment evaluated the effect of intracoronary short term low dose diltiazem administration given immediately with postischemic myocardial reperfusion. Yorkshire swine underwent thoracotomy and 50 min of left anterior descending (LAD) occlusion, followed by 3 h of reperfusion. In the first group, diltiazem (2.5 mg diluted in 60 cc saline) was infused into the LAD over 12 min, beginning with the onset of reperfusion (n=8). In the second group, animals received saline instead of diltiazem and served as controls (n=6). Infarct size was 0.13+/-0.06 g/kg of body weight for diltiazem group, and 0.42+/-0.04 g/kg for controls (P=0.01). CONCLUSIONS: Short-term low dose diltiazem delivered exclusively during early reperfusion can significantly diminish infarct size in swine. Local intracoronary diltiazem may be valuable adjunct in patients subject to myocardial ischemia/reperfusion during coronary artery bypass grafting, primary angioplasty for AMI, or thrombolysis for AMI if given immediately after restoration of coronary blood flow.

Serial changes of the plasma prostanoids during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

The key role of prostanoids has been recognized in patients with ischemic heart disease. However, serial changes of thromboxane and prostacyclin during both brief and prolonged ischemia-reperfusion are poorly known. These plasma prostanoids were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on the level of the stable metabolites of thromboxane (TXB2) and prostacyclin (6-keto-PGF1 alpha) were elucidated. Forty-nine swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. The occlusion phase was associated with a decline of plasma prostanoids, followed by a significant increase during reperfusion. Mg and diltiazem similarly affected plasma prostanoids by reducing TXB2 release at 1 h of reperfusion. There was, however, no effect on plasma 6-keto-PGF1 alpha. The Mac-1 inhibition was associated with stabilization of both antagonistic prostanoids as well. Ability of Mg, diltiazem, and leumedins to favorably modulate plasma prostanoid levels have direct clinical implications for the use of these agents in patients with coronary artery disease.

Dietary coenzyme Q10 supplementation alters platelet size and inhibits human vitronectin (CD51/CD61) receptor expression.

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10, but a comprehensive explanation of its cardioprotective properties is still lacking. One attractive theory links ubiquinone with the inhibition of platelets. The effect of CoQ10 intake on platelet size and surface antigens was examined in human volunteers. Study participants received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days. Receptor expression was measured by flow cytometry with monoclonal murine anti-human antibodies CD9 (p24), CD42B (Ib), CD41b (IIb), CD61 (IIIa), CD41a (IIb/IIIa), CD49b (VLA-2), CD62p (P selectin), CD31 (PECAM-1), and CD51/CD61 (vitronectin). An increase of total serum CoQ10 level (from 0.6 +/- 0.1 to 1.8 +/- 0.3 micrograms/ml; p < 0.001) was found at protocol termination. Fluorescence intensity was higher for the large platelets when compared with the whole platelet population. Significant inhibition of vitronectin-receptor expression was observed consistently throughout ubiquinone treatment. Reduction of platelet size was observed at the end of CoQ10 supplementation. Inhibition of the platelet vitronectin receptor and a reduction of the platelet size are direct evidence of a link between dietary CoQ10 intake and platelets. These findings may not be fully explained by the known antioxidant and bioenergetic properties of CoQ10. Diminished vitronectin-receptor expression and reduced platelet size resulting from CoQ10 therapy may contribute to the observed clinical benefits in patients with cardiovascular diseases.

Could coenzyme Q10 affect hemostasis by inhibiting platelet vitronectin (CD51/CD61) receptor?

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10, ubiquinone). Several mechanisms have been proposed to explain the effects of CoQ10. One attractive theory links ubiquinone with the inhibition of platelets. The effect of CoQ10 intake on platelet surface antigens, and certain hemostatic parameters was examined in 15 humans and 10 swine. Study participants received 100 mg of CoQ10 twice daily in addition to their usual diet for 20 days resulting in a three-fold increase of total serum CoQ10 level. We observed a decline in plasma fibronectin (-20.2%), thromboxane B2 (-20.6%), prostacyclin (-23.2%), and endothelin-1 (-17.9%) level. Significant inhibition of vitronectin receptor expression was observed consistently throughout ubiquinone treatment. Inhibition of the platelet vitronectin receptor is a direct evidence of a link between dietary CoQ10 intake, platelets, and hemostasis. These findings may contribute to the observed clinical benefits by a diminished incidence of thrombotic complications in such patients.

Hemostatic changes after early versus late intracoronary magnesium during acute myocardial infarction in swine.

There has been some debate regarding the benefit of magnesium (Mg) in the treatment of acute myocardial infarction (AMI) because of conflicting results from recent clinical trials. Several different hypotheses have been advanced to explain the cardioprotective properties of Mg, including the influence of the timing of Mg administration during AMI. This experiment was designed to assess the effect of intracoronary Mg on certain hemostatic parameters that are known to change during an AMI. Yorkshire swine underwent thoracotomy and 50 min left anterior descending artery (LAD) occlusion, followed by 3 h of reperfusion. In the early group, 250 mg of MgSO4 was delivered at the onset of reperfusion (n = 6, Mg-early group). In the second group, MgSO4 was given after 1 h of reperfusion (n = 6, Mg-late group). Six animals received saline instead of Mg and served as controls. The dynamics of plasma antithrombin-III (AT-III), protein C, total protein S, fibronectin, endothelin-1 (ET-1), as well as the stable metabolites of thromboxane (TXB2) and prostacyclin (6-keto-PGFla) were determined at baseline, twice during occlusion, and three times during reperfusion. Mg given at reperfusion onset was associated with a diminished ET-1 (32.9%), decreased fibronectin level (21.7-25.2%), and increased protein C concentrations (31.9-52.3%) when compared with both the control and late Mg group. In summary, intracoronary Mg administered at the onset of reperfusion favorably influenced hemostasis in swine. The beneficial effects of early Mg supplementation in an expanding array of clinical conditions, including AMI, may be directly related to the improved hemostatic profile in such patients.

Changes in the haemostatic profile during magnesium deficiency in swine.

Epidemiological studies of populations living in areas of low magnesium (Mg) intake have consistently shown a higher cardiovascular morbidity. Several hypotheses have been advanced to explain the cardioprotective properties of magnesium. Few studies, however, have analysed the relation of magnesium to haemostasis. The overall purpose of this project was to assess the association between certain haemostatic variables and magnesium deficiency. This experiment was designed to assess the effect of magnesium deficiency on various haemostatic variables which may relate to cardiovascular morbidity. Twelve female Yorkshire swine were fed for seven weeks on an Mg-sufficient or an Mg-deficient diet. Blood samples were obtained at baseline and after the termination of feeding in order to evaluate platelet aggregability and concentrations of antithrombin-III (AT-III), protein C, total protein S, fibronectin, endothelin-1 (ET-1), as well as the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1 alpha). In animals on an Mg-sufficient diet, there were no significant differences in any of the investigated haemostatic variables. In the Mg-deficient group, a significant decrease in serum magnesium was noted after the feeding period (from 2.0 +/- 0.1 to 1.3 +/- 0.1; P < 0.01). Mg-deficient swine showed significant increases in ADP-induced (33.3 per cent and 59.6 per cent) and collagen-induced (36.6 per cent) platelet aggregation, and decreased plasma antithrombin-III (17.7 per cent) and protein S (14.4 per cent) when compared to baseline. Plasma concentrations of TxB2 (28.7 per cent), protein C (57.2 per cent), and ET-1 (74.9 per cent) were dramatically increased. There were no significant differences in plasma fibronectin and 6-keto-PGF1 alpha levels in the magnesium-depleted animals. We conclude that magnesium deficiency is associated with significant proaggregatory and coagulation alterations. This may contribute to the increased cardiovascular morbidity found in magnesium-deficient populations. The beneficial effects of magnesium supplementation in an expanding array of clinical conditions including cardiovascular disease may, in part, be related to the improved haemostatic profile in such patients.

Intracoronary magnesium and diltiazem affect to a similar extent certain hemostatic factors during acute myocardial infarction in swine.

The use of calcium antagonists and magnesium (Mg) in the treatment of acute myocardial infarction is controversial. We compared changes in hemostasis during acute myocardial infarction after either low-dose intracoronary Mg or diltiazem infusion in 20 Yorkshire swine undergoing thoracotomy and coronary artery occlusion for 50 min, followed by 3 h of reperfusion. The first group received MgSO4 (250 mg), delivered at the onset of reperfusion, the second group received diltiazem (2.5 mg) at the beginning of reperfusion. Six controls received saline. Plasma antithrombin III, protein C, total protein S, fibronectin, endothelin 1, and metabolites of thromboxane and prostacyclin were measured at baseline, twice during occlusion, and three times during reperfusion. Compared to controls, Mg and diltiazem infusion diminished endothelin 1 (32.9 vs. 34.5%) and fibronectin. (21.7 vs. 23.2%), but increased protein C (31.9 vs. 29.3%). Intracoronary Mg, like diltiazem, improved hemostasis in swine.

Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 +/- 3.38% to 138.1 +/- 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 +/- 1.8% to 55.7 +/- 1.4%) reaching a peak (64.5 +/- 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 +/- 3.4% to 61.0 +/- 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 +/- 2.2% to 46.7 +/- 1.0%), followed by an increase during late reperfusion (59.2 +/- 1.5%). Contrarily, protein C increased during occlusion and early reperfusion (from 44.7 +/- 2.6% to 79.4 +/- 2.4%), but declined to 49.6 +/- 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.

Hemostatic changes after dietary coenzyme Q10 supplementation in swine.

Improved cardiovascular morbidity and mortality have been observed in several clinical studies of dietary supplementation with coenzyme Q10 (CoQ10). We elucidated the effect of CoQ10 on certain hemostatic parameters that may influence the progression of heart disease. Twelve Yorkshire swine were randomized to receive diet supplementation with either CoQ10 or placebo for 20 days. Blood samples were obtained at baseline and at the end of the feeding period. At the end of the protocol, there were no significant differences in hemostatic parameters in the placebo group. A significant increase in total serum CoQ10 level (from 0.39 +/- 0.06 to 0.96 +/- 0.04 microgram/ml, p < 0.001) was noted after the feeding period in the CoQ10-supplemented group. We observed significant inhibition of ADP-induced platelet aggregation (-9.9%) and a decrease in plasma fibronectin (-20.2%), thromboxane B2 (TXB2, -20.6%), prostacyclin (-23.2%), and endothelin-1 (ET-1, -17.9%) level. There were no changes in the plasma concentrations of the natural antithrombotics [antithrombin-III (AT-III), protein S, and protein C] after CoQ10 supplementation. CoQ10 supplementation in a dose of 200 mg daily is associated with mild antiaggregatory changes in the hemostatic profile. Clinical beneficial effects of CoQ10 may be related in part to a diminished incidence of thrombotic complications.

Mac-1 inhibitor affects certain hemostatic parameters during myocardial stunning in swine.

Myocardial stunning (MS) is a transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. NPC 15669 is a leumedin, which inhibits leukocyte adhesion to the endothelium by blocking Mac-1 upregulation. The effect of NPC 15669 supplementation on the hemostasis during MS is unknown. We linked the potential changes in the hemostasis with NPC 15669 therapy during mild MS. Twelve Yorkshire swine underwent coronary artery occlusion for 8 min followed by 90 min of reperfusion. NP 15669 (10 mg/kg loading dose followed by constant infusion a 6 mg kg-1 h-1) was administered to 6 of the animals; another swine received saline and served as the controls. Concentrations of antithrombin III (AT-III), protein C, total protein S, fibronectin, endothelin 1 (ET-1) and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1 alpha) were measured in the systemic circulation. NPC 15669 therapy was associated with diminished ET-1 (37.4%) and 6-keto-PGF1 alpha (47.1%) levels and increased fibronectin (77.6%) concentrations during MS. There were no changes in the plasma concentrations of TxB2, total protein S, protein C and AT-III in the NPC 15669 group when compared with controls. Mild MS in associated with substantial changes in the hemostatic profile. NPC 15669 administration in a swine model of MS affects certain hemostatic parameters. These data provide support for the involvement of cellular mechanisms in the pathogenesis of MS. The ability of leumedins to modulate hemostasis may have implications for their use in cardiovascular disease.

Timing of magnesium therapy affects experimental infarct size.

BACKGROUND: Controversy exists regarding the use of magnesium in the treatment of acute myocardial infarction (AMI) because of apparent conflicting results from clinical trials. One hypothesis to explain the various clinical observations proposes that the timing of magnesium administration significantly influences its therapeutic effect; ie, supraphysiological levels of Mg2+ must be present at the time of reperfusion for magnesium to produce clinical benefit. METHODS AND RESULTS: These experiments evaluated the effect of varying the timing of magnesium administration during AMI. Female Yorkshire swine (34 to 42 kg) underwent thoracotomy and 50 minutes of left anterior descending coronary artery (LAD) occlusion, followed by 3 hours of reperfusion. In the first group, MgSO4 (250 mg of magnesium diluted in 60 cm3 saline) was infused into the LAD over 12 minutes, beginning immediately with the onset of reperfusion (n = 6, Mg-early group). In the second group, MgSO4 was given after 1 hour of reperfusion (n = 6, Mg-late group). Six pigs received saline instead of magnesium and served as the control group. Lethal arrhythmias were significantly reduced in the Mg-early group. Infarct size was determined by vital staining. Infarct size was 0.16 +/- 0.05 g/kg body wt (Mg-early), 0.35 +/- 0.08 g/kg (Mg-late), and 0.42 +/- 0.04 g/kg for the control group. Compared with the control group, significant (P = .029) reduction in infarct size occurred in the Mg-early group but not in the Mg-late group. CONCLUSIONS: We conclude that intracoronary MgSO4 delivered during reperfusion can significantly diminish infarct size in swine, but the timing of administration is critical.

Reactivity of coronary arteries in relation to serum magnesium levels in patients with ischaemic heart disease--a quantitative coronary angiographic study.

The aim of the present study was to evaluate the relationship between coronary vascular tone and serum magnesium concentration in patients with ischaemic heart disease. Thirty-seven patients were subjected to intracoronary injection of 200 micrograms nitroglycerine after discontinuation of anti-anginal medication for 24 h (group I, n = 23), except if they received calcium channel blockers (group II, n = 14). Coronary angiographic images were acquired before and 2 min after the nitroglycerine injection. Using quantitative coronary arteriography, the luminal diameter of one middle-sized non-stenotic coronary artery segment in each patient was measured before and after nitroglycerine injection, and the percentual increase was computed. In group I, coronary artery diameter changed from 3.0 +/- 0.7 to 3.5 +/- 0.6 mm (mean +/- SD), representing a 16.3 per cent increase. As expected, a more blunted response was observed in group II (from 3.5 +/- 0.8 to 3.7 +/- 1.0 mm, 6.5 per cent increase). However, neither of the groups displayed significant correlation between serum magnesium levels and the measured response to intracoronary nitroglycerine. In conclusion, this study fails to provide any correlation between serum magnesium levels within the normal physiological range and coronary vascular reactivity in patients with ischaemic heart disease.

Magnesium deficiency prolongs myocardial stunning in an open-chest swine model.

The effect of magnesium deficiency on postischemic myocardial dysfunction (myocardial stunning) in an open-chest swine model was studied. Twelve swine were assigned either to low magnesium diet or control diet. Myocardial stunning was assessed by measuring regional wall thickening by epicardial Doppler before and after brief occlusion (8 min) of the left anterior descending coronary artery. Serum magnesium levels decreased significantly in the experimental group only. Glutathione levels were 42.6% lower in the magnesium deficient swine than in controls. Stunning time was significantly prolonged from 32.8 +/- 3.1 min in the control group to 43.8 +/- 4.6 min in the hypomagnesemic swine. In conclusion, magnesium deficiency is associated with prolonged recovery from myocardial stunning.