[Application of radial artery in arterialized coronary artery bypass grafting in Chinese patients].

Objective: To summarize the application of radial artery (RA) as the second arterial graft in coronary artery bypass grafting (CABG). Methods: From January 1, 2015 to June 11, 2019, the clinical data of all patients undergoing CABG in TEDA International Cardiovascular Hospital was retrospectively reviewed. The patients who underwent RA grafting were included. The application of RA, internal mammary artery (IMA) and the saphenous vein, their target vessels, and the operative results were analyzed. Results: A total of 2 901 patients underwent CABG. Of those, 208 patients (7.2%) had RA grafting, with 197 males and 11 females. The average age was (53±8) years old and the average grafts per patient was 3.79. The target vessel for RA was first obtuse marginal (OM, 102 cases), first diagonal (50 cases), right coronary artery (RCA) or posterior descending artery (PDA) (40 cases), intermediate (22 cases), respectively. Among those, 172 were single distal anastomosis with the proximal end anastomosed to the ascending aorta (168 cases), saphenous vein (SV) graft (3 cases) and IMA (1 case). Seventy-two patients accept sequential grafting with the proximal to the ascending aorta (58 cases), SV graft (13 cases) and IMA (1 case). The left IMA was mainly anastomosed to left descending artery (LAD) (188 cases) and diagonal (10 cases). The target vessels for SV were remaining coronary arteries when the IMA and RA were used. The operative time was (5.0±1.5) h. The hospital stay was (17.4±6.4) d. There were 6 cases undergoing exploratory thoracotomy for bleeding (5 cases) or hemodynamic instability due to ventricular arrhythmia (1 case). There was no death. All patients were successfully discharged. Conclusions: Use of the RA and IMA with additional SV for CABG exhibits good results in the Chinese patients. Currently available clinical protocols are effective and safe.

[Determination of trace gallium by graphite furnace atomic absorption spectrometry in urine].

OBJECTIVE: To establish a method for determination trace gallium in urine by graphite furnace atomic absorption spectrometry (GFAAS). METHODS: The ammonium dihydrogen phosphate was matrix modifier. The temperature effect about pyrolysis (Tpyr) and atomization temperature were optimized for determination of trace gallium. The method of technical standard about within-run, between-run and recoveries of standard were optimized. RESULTS: The method showed a linear relationship within the range of 0.20~80.00 µg/L (r=0.998). The within-run and between-run relative standard deviations (RSD) of repetitive measurement at 5.0, 10.0, 20.0 µg/L concentration levels were 2.1%~5.5% and 2.3%~3.0%. The detection limit was 0.06 µg/L. The recoveries of gallium were 98.2%~101.1%. CONCLUSION: This method is simple, low detection limit, accurate, reliable and reproducible. It has been applied for determination of trace gallium in urine samples those who need occupation health examination or poisoning diagnosis.

Maternal high-fat diet impacts endothelial function in nonhuman primate offspring.

OBJECTIVE: The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model. METHODS: Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age. RESULTS: HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel. CONCLUSION: Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.

Heparin- and basic fibroblast growth factor-incorporated degradable stent: comparison with traditional transmyocardial revascularization.

AIM: We have recently developed a novel method transmyocardial drilling revascularization (TMDR) combined with heparinized bFGF-incorporating degradable tubular stent implantation to revascularize ischemic myocardium. The aim of the present study was to compare the effect of this new method on left ventricular (LV) remodeling and global function to traditional transmyocardial revascularization (TMR) in acute myocardial ischemia. METHODS: Eighteen miniswine underwent ligation of the left anterior descending (LAD) at the mid-third and were divided into three groups (N.=6 in each group): no treatment (control), TMDR (T), and TMDR+stent implantation (TS) groups. Two channels with 3.5 mm in diameter were established (T and TS groups), followed by implantation of two stents (TS group). LV function, myocardial perfusion, expression of von Willebrand factor (vWF), transforming growth factor-ß3 (TGF-ß3), vascular endothelial growth factor (VEGF), interleukin-1beta (IL-1ß), vascular density, and histologic and morphologic analyses were evaluated at different time-points. RESULTS: Six weeks post-treatment, there were no differences between T and control groups. TS group showed significant improvement compared to T group as to: expressions of TGF-ß3, VEGF, vWF and IL-1ß (P<0.001), neovascular density (2.561±391 vs. 6.201±443 pixels/hpf, P<0.001), myocardial viability (18.913±2775 vs. 94.800±14.076 pixels/hpf, P<0.001), and dp/dtmax (1.735±161 vs. 2.242±223 mmHg/s, P<0.001), Further, there were significant decreases in changes of Mass Defect Percent (2.05±0.22% vs. -1.79±0.45%, P<0.001) and LV end diastolic volume (164.83±10.74 vs. 147.00±7.32 mL, P=0.048) in the TS group. CONCLUSION: TMDR and stent implantation is more effective in enhancement of myocardial viability, improvement of global LV function, and attenuation of LV remodeling than TMDR.

Tetramethylpyrazine-2'-O-sodium ferulate attenuates blood-brain barrier disruption and brain oedema after cerebral ischemia/reperfusion.

Disruption of blood-brain barrier (BBB) and subsequent oedema are major causes of the pathogenesis in ischaemic stroke with which the current clinical therapy remains unsatisfied. In this study, we examined the therapeutic effect of tetramethylpyrazine-2'-O-sodium ferulate (TSF)-a novel analogue of tetramethylpyrazine in alleviating BBB breakdown and brain oedema after cerebral ischaemia/reperfusion (I/R). Then, we explored the potential mechanism of the protection on BBB disruption in cerebral I/R rat models. Male Sprague-Dawley rats (250-300 g) were subjected to 120 min middle cerebral artery occlusion (MCAO), followed by 48 h reperfusion. TSF (10.8, 18 and 30 mg kg-1) and ozagrel (18 mg kg-1) were administrated by intravenous injection immediately for the first time and then received the same dose every 24 h for 2 days. We found that TSF treatment significantly attenuated the cerebral water content, infarction volume and improved neurological outcomes in MCAO rats compared to I/R models. Moreover, we investigated the effect of TSF on the BBB for that cerebral oedema is closely related to the permeability of the BBB. We found that the permeability of BBB was improved significantly in TSF groups compared to I/R model group by Evans blue leakage testing. Furthermore, the expressions of tight junction (TJ) proteins junction adhesion molecule-1 and occludin significantly decreased, but the protein expression of matrix metalloproteinase-9 (MMP-9) and aquaporin 4 (AQP4) increased after cerebral I/R, all of which were alleviated by TSF treatment. In conclusion, TSF significantly reduced BBB permeability and brain oedema, which were correlated with regulating the expression of TJ proteins, MMP-9 and AQP4. These findings provide a novel approach to the treatment of ischaemic stroke.

Comparison of nitric oxide release and endothelium-derived hyperpolarizing factor-mediated hyperpolarization between human radial and internal mammary arteries.

BACKGROUND: Arterial grafts for CABG have been used increasingly, and the radial artery (RA) has become a preferable graft, secondary to the internal mammary artery (IMA). In the present study, we investigated and compared NO release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization for IMA and RA. METHODS AND RESULTS: IMA and RA segments taken from CABG patients were placed in an organ chamber. An NO-sensitive electrode (to directly measure NO release) or intracellular glass microelectrode (to measure membrane potential) was used to study NO or EDHF in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with indomethacin (a cyclooxygenase inhibitor), N(G)-nitro-L-arginine (an NO synthase inhibitor), and oxyhemoglobin (an NO scavenger). The resting membrane potential of the smooth muscle cells of IMA and RA was -58+/-0.84 (n=61) and -61+/-1.3 (n=46) mV, respectively (P=0.03). BK-induced EDHF-mediated hyperpolarization in the IMA was significantly greater than that in RA (BK 10(-)(7) mol/L: -10.9+/-1.5 [n=7] versus -5.8+/-0.9 [n=6] mV, P=0.04). The basal (16.8+/-1.9 versus 11.1+/-1.0 nmol/L, n=12, P=0.02) and stimulated releases of NO in IMA were significantly greater for BK (44.3+/-4.0 versus 25.8+/-3.6 nmol/L, n=8, P=0.004) and lasting longer for ACh (9.5+/-2.0 versus 6.6+/-3.6 minutes, n=12, P=0.03) than those in RA. CONCLUSIONS: The basal and stimulated releases of NO and EDHF-mediated hyperpolarization in the IMA are significantly greater than that in the RA. The lower capacity of NO release may contribute to the susceptibility of RA to the perioperative vasospasm and may have an impact on the long-term graft patency.

Difference in endothelium-derived hyperpolarizing factor-mediated hyperpolarization and nitric oxide release between human internal mammary artery and saphenous vein.

BACKGROUND: The greater nitric oxide (NO) release that occurs in the internal mammary artery (IMA) when compared with the saphenous vein (SV) has been suggested by more endothelium-dependent relaxation in the IMA or measured by bioassay; however, no direct measurement of NO- or endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization has been reported. The present study measured such hyperpolarization, as well as NO release, in these vessels. METHODS AND RESULTS: IMA (n=46) and SV (n=61) segments taken from patients undergoing coronary surgery were studied in the organ chamber. Hyperpolarization (by intracellular glass microelectrode) and NO release (by NO-sensitive electrode) in response to acetylcholine and bradykinin, with and without incubation with N(G)-nitro-L-arginine, indomethacin, and oxyhemoglobin, were measured. The resting membrane potential of the smooth muscle cells from the IMA (58+/-0.8 mV; n=15) was higher than that in those from the SV (-62+/-0.9 mV; n=23; P:=0.0001). The EDHF-mediated hyperpolarization induced by acetylcholine (10(-5) mol/L: -9.4+/-1.5 mV in IMA, n=10, versus -4. 5+/-1.0 mV in SV, n=17; P:<0.01) and bradykinin (10(-7) mol/L: -10. 9+/-1.5 mV in IMA, n=8, versus -5.1+/-0.5 mV in SV, n=8; P:<0.01) and the basal release of NO (16.8+/-1.6 nmol/L in IMA, n=13, versus 9.9+/-2.8 nmol/L in SV, n=13; P:<0.001) were significantly greater in the IMA than in the SV. The duration of acetylcholine- and bradykinin-induced NO release was longer in the IMA than in the SV. CONCLUSIONS: The basal release of NO and EDHF-mediated hyperpolarization were significantly greater in the IMA than in the SV. In addition, the duration of the stimulated release of NO was longer in the IMA than in the SV. These differences may contribute to the superior long-term patency of IMA grafts.

Effects of biatrial pacing in prevention of postoperative atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Atrial fibrillation (AF) is common after coronary artery bypass surgery (CABG) and results in prolonged hospitalization. The purpose of this study was to evaluate the efficacy of biatrial pacing in preventing post-CABG AF compared with single-site atrial pacing. METHODS AND RESULTS: A total of 132 patients who had no history of AF and who underwent CABG were randomized to 1 of the following 4 groups: biatrial pacing (BiA), left atrial pacing (LA), right atrial pacing (RA), or no pacing (control) in postoperative period. Overdrive atrial pacing was performed for 5 days. The incidence of AF was significantly reduced in the BiA group (12.5%) compared with the other 3 groups (LA, 36.4%; RA, 33.3%; control, 41. 9%; P<0.05). The mean length of hospital stay was significantly reduced in the BiA group. At baseline, the mean P-wave duration (P(dur)) and dispersion (P(dis)) were not prolonged. BiA pacing resulted in the most significant percentage of reduction in P(dis) when compared with the LA or RA groups (BiA, 42+/-8%; LA, 13+/-6%; RA, 10+/-9%; P<0.05 for BiA versus LA or RA). No significant differences existed in mean P(dur) and P(dis) between patients who developed AF and those who remained in sinus rhythm at baseline. However, only those patients who remained in sinus rhythm had a significant reduction in mean P(dur) and P(dis) after pacing therapy. CONCLUSIONS: Biatrial overdrive pacing is more effective in preventing post-CABG AF than single-site atrial pacing; this therapy also results in a shortened hospital stay. The overall reduction in atrial activation time with BiA pacing was reflected in the reduction in P(dis).

Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L-arginine and indomethacin in coronary circulation.

OBJECTIVE: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.

Comparison of University of Wisconsin and St Thomas' Hospital solutions on endothelium-derived hyperpolarizing factor-mediated function in coronary micro-arteries.

BACKGROUND: It is controversial whether coronary endothelial function is impaired after cold exposure to University of Wisconsin (UW) or St. Thomas' Hospital (ST) solution during heart transplantation. We therefore examined the effects of cold storage of coronary micro-arteries with UW or ST solution on endothelium-derived hyperpolarizing factor (EDHF)-mediated function. METHODS: Porcine and human coronary arteries were immersed in either UW or ST solution at 4 degrees C for 4 hr and then normalized in a wire myograph. RESULTS: In the rings (normalized diameter: 200-500 microM) precontracted by U46619, EDHF-mediated relaxation and hyperpolarization were initiated by bradykinin (BK) or A23187 in the presence of indomethacin and NG-nitro-L-arginine. In the human coronary arteries, the EDHF-mediated relaxation to BK was reduced by UW solution from 53.2+/-5.6% to 24.0+/-2.7% (P=0.006). The reduced EDHF-mediated relaxation occurred concurrently with the decreased hyperpolarization to BK (17.0+/-1.5 vs. 10.5+/-1.1 mV, n=10, P=0.004) or A23187 in porcine coronary arteries. In the control arteries, K+ channel blockers, either glybenclamide or tetraethylammonium reduced the EDHF-mediated relaxation. After exposure to UW solution, the EDHF-mediated relaxation was further significantly inhibited. In contrast, ST solution did not affect these responses. CONCLUSIONS: These results show that in coronary micro-arteries, UW, but not ST, solution impairs the EDHF-mediated function and inhibits the Ca2+-activated and ATP-sensitive K+ channels. Our comparative study suggests that ST solution may be superior to UW solution in preserving the EDHF-related endothelial function of coronary micro-arteries.

Contractility of the human internal mammary artery at the distal section increases toward the end. Emphasis on not using the end of the internal mammary artery for grafting.

The distal section of the internal mammary artery (3 to 4 cm proximal to the bifurcation) is often used for coronary grafting. This part of the artery is more pharmacologically responsive to vasoconstrictor agents than is its midsection. The present study was designed to test the hypothesis that the reactivity of the distal section of the internal mammary artery is inversely correlated to the diameter of the artery. The distal section of the human internal mammary artery was collected from aorta-coronary bypass grafts and studied in organ baths at a length of 3 mm. At the optimal point of the length-tension curves determined by a computer-iterative fitting technique, the diameter at 100 mm Hg, the maximal contraction forces and effective concentration causing 50% of the maximal response to vasoconstrictor agents U46619, potassium chloride, alpha-adrenoceptor agonists norepinephrine, methoxamine, and phenylephrine were recorded or calculated. The maximal relaxation and 50% response to glyceryl trinitrate in phenylephrine-precontracted internal mammary artery segments were also calculated. The contraction force was standardized by the circumference (grams per millimeter). Regression analysis between contraction force and diameter revealed that the contraction force induced by U46619 and potassium chloride was inversely correlated to diameter (r2 = 0.2, p < 0.05 in U46619-induced contraction and r2 = 0.2, p < 0.01 in potassium chloride-induced contraction). The contraction force induced by norepinephrine also had a trend inversely correlated to diameter (r2 = 0.2, p = 0.07). Glyceryl trinitrate-induced relaxation was not correlated to diameter. This study demonstrated that the contractility of the distal section of the internal mammary artery is inversely correlated to the diameter; that is, the smaller the diameter, the greater the tendency for spasm to develop. This suggests that trimming off the distal end of the internal mammary artery as much as possible may be the best way to prevent graft spasm and that superior results of left internal mammary artery grafted to the left anterior descending artery or the use of a "free graft" may be related to the shorter length (distal end is trimmed off) and less contractility of the graft.

Verapamil plus nitroglycerin solution maximally preserves endothelial function of the radial artery: comparison with papaverine solution.

BACKGROUND: Endothelium plays a key role in graft patency. My colleagues and I have developed a verapamil+nitroglycerin solution (balanced to pH 7.4) to prepare the radial artery without mechanical distention or dilation and have reported the efficacy of its antispastic action. This study was designed to investigate whether using this solution as part of the University of Hong Kong protocol to prepare the radial artery is more efficacious than papaverine solution in preserving endothelial function. METHODS: Ring segments of the radial artery taken from 25 patients undergoing coronary artery bypass grafting were studied in organ chambers. The endothelium-dependent relaxation, as the index of endothelial function, was examined by two mechanisms-receptor-mediated relaxation (by acetylcholine) and non-receptor-mediated relaxation (by calcium ionophore A23187) in U46619-induced contraction (10 nmol/L). RESULTS: In the relaxation induced by either acetylcholine (27.3% +/- 5.0% [n = 7] vs 23.9% +/- 3.9% [n = 6],p = 0.6) or A23187 (62.9% +/- 6.0% [n = 13] vs 62.3% +/- 8.4% [n = 6],p = 0.96), there was no significant difference between the control radial arteries and those treated with the verapamil+nitroglycerin solution. In the papaverine-treated rings, acetylcholine-mediated relaxation was abolished (3.3% +/- 2.6% vs 23.9% +/- 3.9%,p < 0.001) and A23187-mediated relaxation was significantly reduced (39.7% +/- 5.2% vs 62.3% +/- 8.4%, p = 0.02) compared with verapamil+nitroglycerin treatment. CONCLUSION: Use of verapamil+nitroglycerin solution to prepare the radial artery maximally preserves endothelial function. In contrast, papaverine impairs this function. Verapamil+nitroglycerin solution may be effectively and safely used to prepare the radial artery for coronary artery bypass grafting.

Comparison among arterial grafts and coronary artery. An attempt at functional classification.

Various arterial conduits have been used for coronary artery bypass grafting. However, arterial grafts are not uniform either in anatomy or in function. Some conduits are more spastic than others and there may be possible differences in long-term patency rates. The diverse biologic characteristics promote a necessity of classification of arterial grafts, which may facilitate the understanding of surgeons of biologic characteristics of various arterial grafts and provide a scientific basis for searching for new grafts. Another important issue is the comparison of reactivity between arterial grafts and coronary arteries. In this study, we aim to compare the pharmacologic reactivity among the human arteries (grafts and coronary arteries) and to classify arterial grafts. Segments of three arterial grafts (gastroepiploic, internal mammary, and inferior epigastric) taken from patients undergoing coronary artery bypass grafting and coronary arteries taken from explanted hearts were studied in organ baths for the contraction to four vasoconstrictors (endothelin-1, thromboxane A2 mimetic U46619, full adrenoceptor agonist norepinephrine, and depolarizing agent potassium) under physiologic pressure. The diameter of the four arteries at a pressure of 100 mm Hg was similar (p > 0.05). However, the gastroepiploic artery contracted to higher forces (9.41 +/- 2.0 gm for endothelin, 11.79 +/- 1.85 gm for U46619, 13.54 +/- 2.7 gm for norepinephrine, and 11.11 +/- 1.97 gm for potassium) than did the coronary artery and internal mammary artery (p < 0.05) for all the tested vasoconstrictors and higher than the inferior epigastric artery for potassium and norepinephrine (p < 0.05). There was no significant difference among the other three arteries (internal mammary artery, inferior epigastric artery, and coronary artery) regarding the maximal contraction force to any vasoconstrictor. No difference was detected in regard to the sensitivity (effective concentration causing 50% of the maximal response) to the vasoconstrictors among the four arteries. This study reveals that among the arterial grafts and the coronary artery, the gastroepiploic artery has the highest contractility to various vasoconstrictors. On the basis of our findings and physiologic and embryologic knowledge we propose a classification for arterial grafts: type I (somatic arteries), type II (splanchnic arteries), and type III (limb arteries). Types II and III are prone to spasm because of higher contractility whereas type I arteries are usually less spastic. This classification may have important clinical implications for the understanding of arterial graft spasm or patency and may be useful in the search for new grafts.

Superiority of hyperpolarizing to depolarizing cardioplegia in protection of coronary endothelial function.

OBJECTIVE: Hyperpolarizing cardioplegia has recently been proposed for myocardial protection. To compare the protective effect of hyperpolarizing cardioplegia and depolarizing (hyperkalemic) cardioplegia on coronary endothelium, we studied porcine coronary arteries in the organ chamber. METHODS: Relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) was used as the index of endothelial function because (1) hyperkalemia without ischemia does not impair the nitric oxide-mediated function according to previous studies and (2) EDHF relaxes vessels by hyperpolarizing the membrane potential. Therefore depolarizing cardioplegia may inhibit this function, but hyperpolarizing cardioplegia may preserve it. EDHF-mediated relaxation was induced by bradykinin and the calcium ionophore A23187 with the presence of indomethacin (7 micromol/L; INN: indometacin), a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine (300 micromol), a nitric oxide biosynthesis inhibitor in U46619 (30 nmol/L)-induced precontraction. The vessels were exposed to either hyperpolarizing cardioplegic solution (the potassium-channel opener aprikalim, 0.1 mmol/L) or depolarizing cardioplegic solution (high potassium concentration, 20 mmol/L for A23187 and 50 mmol/L for bradykinin experiments) for 1 hour with a constant supply of oxygen to exclude the effect of ischemia. RESULTS: EDHF-mediated relaxation was significantly impaired in either A23187 or bradykinin studies (80.1% +/- 7.5% vs 24.9% +/- 14.2%, p = 0.004, n = 8 in each group for A23187, and 71.4% +/- 4.7%, n = 13, vs 40.5% +/- 12.9%, n = 7, p = 0.01, for bradykinin). The effective concentration causing 50% of maximal relaxation was significantly increased in the A23187 experiments with the treatment of hyperkalemia. In contrast, in aprikalim-treated arteries, the EDHF-mediated relaxation induced by either A23187 or bradykinin was unchanged. CONCLUSIONS: We conclude that EDHF-mediated coronary endothelial function is maximally preserved by hyperpolarizing cardioplegia but impaired by depolarizing cardioplegia. These findings support the use of hyperpolarizing cardioplegia in cardiac operations.

Vasorelaxant effect of phosphodiesterase-inhibitor milrinone in the human radial artery used as coronary bypass graft.

OBJECTIVE: The radial artery is a spastic coronary bypass graft. We investigated the effect of the phosphodiesterase III inhibitor milrinone on the human radial artery. METHODS: Radial artery segments (n = 76) taken from 15 patients were studied in an organ chamber. Concentration-relaxation curves for milrinone were established in the radial artery precontracted with 3 vasoconstrictors (phenylephrine, K(+), and U46619). In radial artery rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 micromol/L) for 10 minutes, concentration-contraction curves for the 3 vasoconstrictors were constructed. RESULTS: Milrinone caused a submaximal relaxation in phenylephrine- (98.6% +/- 1.4%), K(+)- (89.1 +/- 4.5%), or U46619- (74.2 +/- 8.0%) precontracted radial arteries at -4.5 log(10) M. The EC(50) was higher against K(+) (-5.85 +/- 0.24 log(10) M, P =.02) or U46619 (-5. 21 +/- 0.61 log(10) M, P =.03) than phenylephrine (-6.68 +/- 0.11 log(10) M). Pretreatment with milrinone depressed the contraction by phenylephrine from 70.0% +/- 7.9% to 23.5% +/- 9.3% (P =.003) and by K(+) from 138.6% +/- 5.8% to 73.0% +/- 13.9% (P =.006) and shifted the EC(50) 3.8-fold higher (P =.03) for phenylephrine and 2.2-fold higher for K(+) (P =.01). Milrinone reduced the U46619 contraction at low concentration (-8.5 log(10) M) but had little effect on the maximal contraction. CONCLUSION: Milrinone is a potent vasodilator for the radial artery, with possibly higher potency in alpha-adrenoceptor- and depolarizing agent K(+)-mediated, but less potency in thromboxane A(2)-mediated, contraction. Because it also has a positive inotropic effect, this vasodilator may be particularly indicated for use in patients receiving radial artery grafts in coronary artery bypass grafting.

Comparative study on calcium channel antagonists in the human radial artery: clinical implications.

OBJECTIVES: The radial artery is spastic, and calcium channel antagonists have been used clinically in the radial artery for their antispastic effects. To choose a proper calcium channel antagonist for such a purpose, we compared the in vitro antispastic effects of 4 clinically used calcium channel antagonists (nicardipine, nifedipine, verapamil, and diltiazem) in the human radial artery. METHODS: Radial artery segments taken from patients undergoing coronary bypass operations were studied in the organ bath. The relaxation by the calcium channel antagonists was compared in the potassium-precontracted (25 mmol/L) radial artery. The inhibitory effect of the calcium channel antagonists at the clinically relevant plasma concentration and a higher concentration was also studied for the calcium channel antagonists. RESULTS: All calcium channel antagonists induced a full relaxation (97.8%-100%, n = 5-7 for each), with higher sensitivity (P =.005, analysis of variance [ANOVA] among the calcium channel antagonists for the effective concentration of the constrictor [or dilator] agent that caused 50% of maximal contraction [or relaxation]) to nifedipine (-7.37 +/- 0. 20 log(10) M) than nicardipine (-6.43 +/- 0.39 log(10) M, P =.1), verapamil (-6.08 +/- 0.13 log(10) M, P =.03), and diltiazem (-5.87 +/- 0.07 log(10) M, P =.01). Pretreatment with the plasma concentration of the calcium channel antagonists (60 nmol/L for diltiazem and 20 nmol/L for the others) inhibited the potassium-induced contraction (n = 6 for each) by nicardipine (from 138.6% +/- 5.8% to 101.4% +/- 7.6%, P =.001) and nifedipine (to 87. 7% +/- 6.8%, P =.0003) but not by verapamil (to 140.3% +/- 15.2%, P =.9) or diltiazem (to 132.8% +/- 7.3%, P =.8), although at higher contractions (-4.5 log(10) M) all 4 calcium channel antagonists abolished the contraction. CONCLUSIONS: Although all calcium channel antagonists have antispastic effects in the radial artery, the vessel has different sensitivities to them. Dihydropyridine derivatives may be the most potent calcium channel antiagonists and therefore are recommended for the clinical use for this purpose.

Characteristics of adrenoceptors in the human radial artery: clinical implications.

OBJECTIVES: The radial artery has been suggested to be spastic. Endogenous and exogenous catecholamines and the use of beta-blockers may be related to radial artery spasm, but the characteristics of adrenoceptors in this artery are unknown. This study was designed to characterize the alpha- and beta-adrenoceptor in the human radial artery. METHODS: Ring segments of the radial artery (n = 59) taken from patients undergoing coronary artery bypass grafting were studied in organ chambers. Alpha-adrenoceptor agonists (norepinephrine, methoxamine, and UK14304) and antagonists (phentolamine hydrochloride [INN: phentolamine], prazosin, and yohimbine) were used to characterize the alpha-adrenoceptor. Beta-adrenoceptor function was studied in U46619-precontracted rings in response to isoproterenol (INN: isoprenaline). RESULTS: Norepinephrine induced 6.9 +/- 0.6 gm (80.6% +/- 6.8% of the contraction by 100 mmol/L KCl), and this was almost fully inhibited by phentolamine hydrochloride (10 micromol/L, p < 0.0001). The contraction force induced by methoxamine (2.9 +/- 0.8 gm) was abolished by 0.5 micromol/L prazosin (p = 0.017). The contraction force induced by UK14304 (1.7 +/- 0.4 gm) was abolished by 1 micromol/L yohimbine. In contrast to the porcine coronary artery used as the control (fully relaxed to isoproterenol), radial artery rings did not have significant relaxation (1.1% +/- 0.8%). CONCLUSIONS: The human radial artery is an alpha-adrenoceptor-dominant artery with little beta-adrenoceptor function. The use of beta-blockers will not likely evoke the spasm of the radial artery. Furthermore, the radial artery has a dominant alpha1-adrenoceptor function, but the postjunctional alpha2-adrenoceptor is also functional. Circulating catecholamines will mainly contract the human radial artery by activation of the alpha1-adrenoceptors and to a lesser extent also by alpha2-adrenoceptors.

Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.

OBJECTIVES: We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time. METHODS: Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine. RESULTS: After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes. CONCLUSIONS: Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.

Impaired endothelium-derived hyperpolarizing factor-mediated relaxation in coronary arteries by cold storage with University of Wisconsin solution.

OBJECTIVES: University of Wisconsin solution is widely used to preserve organs for transplantation, but its effect on the individual endothelium-derived relaxing factors has not been studied. This study was designed to examine the effect of cold storage of the heart with University of Wisconsin solution on relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF). METHODS: Porcine coronary artery rings were studied in organ chambers. Relaxation in response to the EDHFs stimuli bradykinin and A23187 in U46619 (30 nmol/L)-induced precontraction after incubation with University of Wisconsin solution (either at 37 degrees C in the oxygenated organ chamber or at 4 degrees C in a refrigerator for 4 hours) was compared with the control. RESULTS: During the incubation, the coronary tone initially increased transiently (4.8 +/- 0.8 gm) and was subsequently reduced by 10.9 +/- 1.2 gm. Under both normothermia and hypothermia, after the incubation, the relaxation mediated by EDHF significantly decreased (under normothermia: from 68.7% +/- 10.2% to 32.1% +/- 8%, n = 7, p = 0.001, for bradykinin and from 79.9% +/- 8.4% to 56.9% +/- 8.5%, n = 7, p = 0.01, for A23187; under hypothermia and hypoxia: to 18.9% +/- 5.6%, n = 9, p = 0.0005, for bradykinin and 52.7% +/- 7.5%, n = 9, p = 0.03, for A23187). The incubation at normothermia also impaired the coronary smooth muscle contractility to U46619, but this contractility was preserved by cold storage. CONCLUSIONS: During cold storage, University of Wisconsin solution impairs the endothelium-dependent relaxation mediated by EDHF in the coronary circulation. This effect exists after the storage for at least 1 hour.

Pulmonic regurgitation and reconstruction of right ventricular outflow tract with patch. An experimental study.

Twenty-five dogs were divided into three experimental groups. In each animal of Group I (10 dogs), one pulmonary valve leaflet was resected and a monocusp-bearing bovine pericardial patch was sewn into the right ventricular outflow tract. The monocusp was retracted to the patch with plicating sutures, and when the sutures were removed the monocusp became functional. In each animal of Group II (10 dogs), an incision was made in the right ventricular outflow tract along the anterior pulmonary valvular commissure and a bovine pericardial patch of adjustable width (one half, one, or one and one half times the diameter of the pulmonary valve ring) was sewn into the incision. Group III (five dogs) was the control group. During each situation of altered pulmonary valve function, in each experimental animal, the pulmonary blood flow and intracardiac pressures were measured. Pulmonary regurgitation was expressed regurgitant fraction (retrograde flow divided by net forward flow). We reached the following conclusions: In all situations where pulmonary incompetence was created, the regurgitant fraction was related directly to the width of the patch and was usually not more than half of the net forward flow when the width of the patch was less than one and a half times the pulmonary valve ring diameter. Regurgitant fraction was about half of net forward flow when one leaflet had been excised. The index of pulmonary artery diastolic pressure minus right ventricular end-diastolic pressure was sensitive and bore an inverse relationship to the degree of pulmonary regurgitation. An accurately placed monocusp-bearing patch restored pulmonary valve competence after excision of a cusp. In treating patients, we are encouraged to preserve as much pulmonary valve function as possible.