Studies like the ''SHOCK trial'' show that not all patients follow this classic paradigm, since:<ref name="pmid10460813">{{cite journal| author=Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD et al.| title=Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. | journal=N Engl J Med | year= 1999 | volume= 341 | issue= 9 | pages= 625-34 | pmid=10460813 | doi=10.1056/NEJM199908263410901 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10460813 }} </ref><ref name="pmid12538428">{{cite journal| author=Picard MH, Davidoff R, Sleeper LA, Mendes LA, Thompson CR, Dzavik V et al.| title=Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock. | journal=Circulation | year= 2003 | volume= 107 | issue= 2 | pages= 279-84 | pmid=12538428 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12538428 }} </ref><ref name="pmid16043684">{{cite journal| author=Kohsaka S, Menon V, Lowe AM, Lange M, Dzavik V, Sleeper LA et al.| title=Systemic inflammatory response syndrome after acute myocardial infarction complicated by cardiogenic shock. | journal=Arch Intern Med | year= 2005 | volume= 165 | issue= 14 | pages= 1643-50 | pmid=16043684 | doi=10.1001/archinte.165.14.1643 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16043684 }} </ref>
*The the range of elevation of [[systemic vascular resistance]] in this trial was wide, suggesting that the compensatory [[vasoconstriction]] wan't a rule in every patient
*The mean [[ejection fraction]] was also moderately decreased in this trial, showing that other mechanisms besides [[cardiac failure]] were present
*Some of the patients had [[leukocytosis]] and [[fever]], which along with the decreased [[systemic vascular resistance]] suggested [[SIRS]]
These facts have introduced the concept that [[myocardial infarction]] may cause [[SIRS]] and that [[inflammation]] plays a part in the development and persistence of cardiogenic shock, contributing to [[myocardial]] dysfunction and [[vasodilation]]. The possibility of developing [[SIRS]] raises with the increasing permanence in cardiogenic shock.<ref name="ReynoldsHochman2008">{{cite journal|last1=Reynolds|first1=H. R.|last2=Hochman|first2=J. S.|title=Cardiogenic Shock: Current Concepts and Improving Outcomes|journal=Circulation|volume=117|issue=5|year=2008|pages=686–697|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.106.613596}}</ref><ref name="Hochman2003">{{cite journal|last1=Hochman|first1=J. S.|title=Cardiogenic Shock Complicating Acute Myocardial Infarction: Expanding the Paradigm|journal=Circulation|volume=107|issue=24|year=2003|pages=2998–3002|issn=0009-7322|doi=10.1161/01.CIR.0000075927.67673.F2}}</ref><ref name="pmid10636626">{{cite journal| author=Brunkhorst FM, Clark AL, Forycki ZF, Anker SD| title=Pyrexia, procalcitonin, immune activation and survival in cardiogenic shock: the potential importance of bacterial translocation. | journal=Int J Cardiol | year= 1999 | volume= 72 | issue= 1 | pages= 3-10 | pmid=10636626 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10636626 }} </ref>
At the time of the [[cardiac]] injury, the [[myocardium]] releases into [[circulation]] [[cytokines]], particularly during the first 24 to 72 hours after the [[MI]], these will induce the [[enzyme]] [[nitric oxide synthase]], thereby increasing the level of [[nitric oxide]], which will be responsible for [[vasodilation]] and worsening of [[hypotension]], further jeopardizing [[left ventricle]] performance.<ref>{{Cite book | last1 = Hasdai | first1 = David. | title = Cardiogenic shock : diagnosis and treatmen | date = 2002 | publisher = Humana Press | location = Totowa, N.J. | isbn = 1-58829-025-5 | pages = }}</ref><ref name="NeumannOtt1995">{{cite journal|last1=Neumann|first1=F.-J.|last2=Ott|first2=I.|last3=Gawaz|first3=M.|last4=Richardt|first4=G.|last5=Holzapfel|first5=H.|last6=Jochum|first6=M.|last7=Schomig|first7=A.|title=Cardiac Release of Cytokines and Inflammatory Responses in Acute Myocardial Infarction|journal=Circulation|volume=92|issue=4|year=1995|pages=748–755|issn=0009-7322|doi=10.1161/01.CIR.92.4.748}}</ref><ref name="Shah2000">{{cite journal|last1=Shah|first1=A|title=Inducible nitric oxide synthase and cardiovascular disease|journal=Cardiovascular Research|volume=45|issue=1|year=2000|pages=148–155|issn=00086363|doi=10.1016/S0008-6363(99)00316-8}}</ref><ref name="pmid11489778">{{cite journal| author=Feng Q, Lu X, Jones DL, Shen J, Arnold JM| title=Increased inducible nitric oxide synthase expression contributes to myocardial dysfunction and higher mortality after myocardial infarction in mice. | journal=Circulation | year= 2001 | volume= 104 | issue= 6 | pages= 700-4 | pmid=11489778 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11489778 }} </ref><ref name="pmid10736276">{{cite journal| author=Cotter G, Kaluski E, Blatt A, Milovanov O, Moshkovitz Y, Zaidenstein R et al.| title=L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock. | journal=Circulation | year= 2000 | volume= 101 | issue= 12 | pages= 1358-61 | pmid=10736276 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10736276 }} </ref><ref name="pmid17133844">{{cite journal| author=Kaluski E, Hendler A, Blatt A, Uriel N| title=Nitric oxide synthase inhibitors in post-myocardial infarction cardiogenic shock--an update. | journal=Clin Cardiol | year= 2006 | volume= 29 | issue= 11 | pages= 482-8 | pmid=17133844 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17133844 }} </ref> [[NO]] may also form a toxic radical, called [[peroxynitrite]], by combining with [[superoxide]], affecting [[myocardial]] [[contractility]].<ref name="pmid10926876">{{cite journal| author=Ferdinandy P, Danial H, Ambrus I, Rothery RA, Schulz R| title=Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. | journal=Circ Res | year= 2000 | volume= 87 | issue= 3 | pages= 241-7 | pmid=10926876 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10926876 }} </ref> Among these released [[cytokines]] during cardiogenic shock, are [[interleukin-6]] and [[tumor necrosis factor]]. In the case of [[IL-6]], this specific [[cytokine]] is correlated with the degree of [[organ failure]] and therefore [[mortality]].<ref name="pmid16775569">{{cite journal| author=Geppert A, Dorninger A, Delle-Karth G, Zorn G, Heinz G, Huber K| title=Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction. | journal=Crit Care Med | year= 2006 | volume= 34 | issue= 8 | pages= 2035-42 | pmid=16775569 | doi=10.1097/01.CCM.0000228919.33620.D9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16775569 }} </ref> These [[inflammatory]] mediators, among other actions, are responsible for the release of [[BNP]], which makes the levels of [[BNP]] good markers, not only for the level of [[inflammation]], but also to evaluate [[hemodynamic]] decompensation.<ref name="pmid16763507">{{cite journal| author=Rudiger A, Gasser S, Fischler M, Hornemann T, von Eckardstein A, Maggiorini M| title=Comparable increase of B-type natriuretic peptide and amino-terminal pro-B-type natriuretic peptide levels in patients with severe sepsis, septic shock, and acute heart failure. | journal=Crit Care Med | year= 2006 | volume= 34 | issue= 8 | pages= 2140-4 | pmid=16763507 | doi=10.1097/01.CCM.0000229144.97624.90 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16763507 }} </ref>
Other [[circulatory]] factors, such as [[procalcitonin]], [[complement]] and [[CRP]], have been reported in some studies to contribute to the development of [[SIRS]] in cardiogenic shock.<ref name="pmid12925454">{{cite journal| author=Granger CB, Mahaffey KW, Weaver WD, Theroux P, Hochman JS, Filloon TG et al.| title=Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial. | journal=Circulation | year= 2003 | volume= 108 | issue= 10 | pages= 1184-90 | pmid=12925454 | doi=10.1161/01.CIR.0000087447.12918.85 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12925454 }} </ref><ref name="pmid17200474">{{cite journal| author=APEX AMI Investigators. Armstrong PW, Granger CB, Adams PX, Hamm C, Holmes D et al.| title=Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial. | journal=JAMA | year= 2007 | volume= 297 | issue= 1 | pages= 43-51 | pmid=17200474 | doi=10.1001/jama.297.1.43 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17200474 }} </ref>
Besides the aforementioned macrocirculatory changes in cardiogenic shock, which may also be seen in [[septic shock]], it is important to mention that [[microcirculation|microcirculatory]] abnormalities, caused in part by the [[inflammatory]] cascades, play an important part in the [[pathogenesis]] of [[organ failure]] as well.<ref name="pmid14691425">{{cite journal| author=De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL| title=Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. | journal=Am Heart J | year= 2004 | volume= 147 | issue= 1 | pages= 91-9 | pmid=14691425 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14691425 }} </ref><ref name="pmid12091178">{{cite journal| author=De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL| title=Microvascular blood flow is altered in patients with sepsis. | journal=Am J Respir Crit Care Med | year= 2002 | volume= 166 | issue= 1 | pages= 98-104 | pmid=12091178 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12091178 }} </ref><ref name="pmid17095120">{{cite journal| author=Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL et al.| title=Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. | journal=Ann Emerg Med | year= 2007 | volume= 49 | issue= 1 | pages= 88-98, 98.e1-2 | pmid=17095120 | doi=10.1016/j.annemergmed.2006.08.021 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17095120 }} </ref>
An important number of patients in cardiogenic shock complicating myocardial infarction (around 3/4), develop it after hospital admission.[1][2] In some of these patients, it is reported that the development of shock, particularly in high risk patients, is related to the use of certain classes of medications, used to treat the MI, these include:[3][4][5][6]
Diuretics, as a cause or aggravating factor. This is due to the fact that pulmonary edema is a common complication of cardiogenic shock, leading to a decrease of circulating plasma volume, particularly in patients with prior heart failure. After the administration of high-dose diuretics, the plasma volume will further decline.
Excess fluid administration, in the case of right ventricular myocardial infarction, the excess volume loading in these patients may also lead or contribute to the development of shock.
Myocardial infarction or ischemia lead to production of superoxide radicals which combine with nitrous oxide to form perioxinitrite which in turn causes myocardial depression and hypotension.
The Pathophysiologic "Spiral" of Cardiogenic shock
Among patients with acute MI, there is often a downward spiral of hypoperfusion leading to further ischemia which leads to a further reduction in cardiac output and further hypoperfusion. The lactic acidosis that develops as a result of poor systemic perfusion can further reduce cardiac contractility. Reduced cardiac output leads to activation of the sympathetic nervous system, and the ensuing tachycardia that develops further exacerbates the myocardial ischemia. The increased left ventricular end diastolic pressures is associated with a rise in wall stress which results in further myocardial ischemia. Hypotension reduces epicardial perfusion pressure which in turn further increases myocardial ischemia.
Patients with cardiogenic shock in the setting of STEMI more often have multivessel disease, and myocardial ischemia may be present in multiple territories. It is for this reason that multivessel angioplasty may be of benefit in the patient with cardiogenic shock. Non-culprit or remote territories may also exhibit myocardial stunning in response to an ischemic insult which further reduces myocardial function. The pathophysiology of myocardial stunning is multifactorial and involves calcium overload in the sarcolemma and "stone heart" or diastolic dysfunction as well as the release of myocardial depressant substances. Areas of stunned myocardium may remain stunned after revascularization, but these regions do respond to inotropic stimulation. In contrast to stunned myocardium, hibernating myocardium does respond earlier to revascularization.
The multifactorial nature of cardiogenic shock can also be operative in the patient with critical aortic stenosis who has "spiraled": There is impairment of left ventricular outflow, with a drop in cardiac output there is greater subendocardial ischemia and poorer flow in the coronary arteries, this leads to further left ventricular systolic dysfunction, given the subendocardial ischemia, the left ventricle develops diastolic dysfunction and becomes harder to fill. Inadvertent administration of vasodilators and venodilators may further reduce cardiac output and accelerate or trigger such a spiral.
Pathophysiologic Mechanisms to Compensate for Cardiogenic shock
Cardiac output is the product of stroke volume and heart rate. In order to compensate for a reduction in stroke volume, there is a rise in the heart rate in patients with cardiogenic shock. As a result of the reduction in cardiac output, peripheral tissues extract more oxygen from the limited blood that does flow to them, and this leaves the blood deoxygenated when it returns to the right heart resulting in a fall in the mixed venous oxygen saturation.
Pathophysiology of Multiorgan Failure
The poor perfusion of organs results in hypoxia and metabolic acidosis. Inadequate perfusion to meet the metabolic demands of the brain, kidneys and heart leads to multiorgan failure.
↑Jeger, R. V. (2006). "Emergency revascularization in patients with cardiogenic shock on admission: a report from the SHOCK trial and registry". European Heart Journal. 27 (6): 664–670. doi:10.1093/eurheartj/ehi729. ISSN0195-668X.